Podcasts about na k atpase

Differences in ion concentrations inside and outside a cell cause a difference in the charge of the intracellular and extracellular environments. This electrical polarization of a cell relative to its environment is referred to as cellular membrane potential. This potential serves as an energy source for a variety of cellular functions and as a way for excitable cells like muscle cells and neurons to communicate their signals. A cell controls its membrane potential by regulating the concentration of multiple ions and other charged particles. Let's take a closer look at the biochemistry behind the cell membrane potential. After listening to this AudioBrick, you should be able to: Define equilibrium and describe the forces at work on ions across a biological membrane. Discuss the importance of the Nernst equation and equilibrium potentials. Describe the importance of Na-K-ATPase in relation to the resting membrane potential (Vr). Describe the nonequilibrium steady-state (NESS). Define and discuss the chord conductance equation. You can also check out the original brick from our Cellular Biology collection, which is available for free. Learn more about Rx Bricks by signing up for a free USMLE-Rx account: www.usmle-rx.com You will get 5 days of full access to our Rx360+ program, including nearly 800 Rx Bricks.  After the 5-day period, you will still be able to access over 150 free bricks, including the entire collections for General Microbiology and Cellular and Molecular Biology. *** If you enjoyed this episode, we'd love for you to leave a review on Apple Podcasts.  It helps with our visibility, and the more med students (or future med students) listen to the podcast, the more we can provide to the future physicians of the world. Follow USMLE-Rx at: Facebook: www.facebook.com/usmlerx Blog: www.firstaidteam.com Twitter: https://twitter.com/firstaidteam Instagram: https://www.instagram.com/firstaidteam/ YouTube: www.youtube.com/USMLERX Learn how you can access over 150 of our bricks for FREE: https://usmlerx.wpengine.com/free-bricks/

Dr. Mike Todorovic, medical educator and science communicator extraordinaire, joins The Curious Clinicians to discuss the Na+/K+ ATPase pump ("the most important enzyme in the human body") and his approach to digital medical education. Watch this episode on our new YouTube channel here, and read the show notes here! Click here to obtain AMA PRA Category 1 Credits™ (0.5 hours), Non-Physician Attendance (0.5 hours), or ABIM MOC Part 2 (0.5 hours). Dr. Matt & Dr. Mike's podcast: https://drmattdrmike.com.au/dr-matt-mikes-medical-podcast/ Dr. Matt & Dr. Mike's YouTube channel: https://www.youtube.com/@DrMattDrMike/featured

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2023.04.28.538698v1?rss=1 Authors: Chlebanowska, P., Szlaga, A., Tejchman-Skrzyszewska, A., Kot, M., Konieczny, P., Skrzypek, K., Muszynska, A., Sobocinska, M., Golebiowska, K., Labaj, P., Blasiak, A., Majka, M. Abstract: Parkinson disease is the second most common neurodegenerative disease defined by presence of Lewy bodies and the loss of dopaminergic neurons in the substantia nigra pars compacta (SNc). There are three types of PD - familial, early-onset and idiopathic. Idiopathic PD (IPD) accounts for approximately 90% of all PD cases. Mitochondrial dysfunction accompanies the pathogenesis of Parkinson's disease. Loss of mitochondrial function increases oxidative stress and calcium buffering, which in turn hinders the production of ATP and disrupts the functioning of dopaminergic neurons. The main barrier in PD research was the lack of proper human models to study the mechanisms of PD development and progression. Using induced pluripotent stem (iPS) cells we generated patient-specific dopaminergic neurons. We observed differences in the mitochondria fitness but not differences in mitochondria mass, morphology or membrane potential. Expression of OXPHOS mitochondrial complexes were lower in PD patients in comparison to control group what resulted in changes in mitochondria respiratory status. We observed also lower expression levels of Na+/K+-ATPase subunits and ATP-sensitive K+ (K-ATP) channel subunits. The lower oxygen consumption rate and extracellular acidification rate values were observed in dopaminergic progenitors and iPSC from PD patients compared to the control group. Importantly, observed decrease in the availability of ATP and in the energy consumption, as well as changes in acidification, may constitute contributing factors to the observed reduced neuronal excitability of PD patients dopaminergic neurons. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2023.04.07.535995v1?rss=1 Authors: Kalia, M., Ligtenstein, S. L. B., Meijer, H. G. E., van Putten, M. J. A. M. Abstract: Normal brain function depends on continuous cerebral blood flow for the supply of oxygen and glucose, and is quickly compromised in conditions where the metabolic demand cannot be met. Insufficient cerebral perfusion can result in ischemic stroke, with symptoms ranging from loss of motor or language function to coma, depending on the brain areas affected. Cerebral ischemia also results in changes in the electroencephalogram. Initially, a reduction of the frequency of the rhythms occurs. Depending on the depth and duration of energy deprivation, this eventually leads to the disappearance of all rhythmic activity. Here, we study the relationship between electroencephalogram (EEG) phenomenology and cellular biophysical principles using a model of interacting thalamic and cortical neural masses coupled with energy-dependent synaptic transmission. Our model faithfully reproduces the characteristic EEG phenomenology during acute cerebral ischemia and shows that synaptic arrest occurs before cell swelling and irreversible neuronal depolarization. The early synaptic arrest is attributed to ion homeostatic failure due to dysfunctional Na+/K+-ATPase. Moreover, we show that the excitatory input from relay cells to the cortex controls rhythmic behavior. In particular, weak relay-interneuron interaction manifests in burst-like EEG behavior immediately prior to synaptic arrest. We corroborate our observations with human EEG data from patients undergoing carotid endarterectomy and patients after cardiac arrest with a postanoxic encephalopathy. The model thus reconciles the implications of stroke on a cellular, synaptic and circuit level and provides a basis for exploring other multi-scale therapeutic interventions. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2022.11.25.517972v1?rss=1 Authors: Maurizi, E., Merra, A., Macaluso, C., Schiroli, D., Pellegrini, G. Abstract: Human corneal endothelial cells are organized in a tight mosaic of hexagonal cells and serve a critical function in maintaining corneal hydration and clear vision. Regeneration of the corneal endothelial tissue is hampered by its poor proliferative capacity, which is partially retrieved in vitro, albeit only for a limited number of passages before the cells undergo mesenchymal transition (EnMT). Although different culture conditions have been proposed in order to delay this process and prolong the number of cell passages, EnMT has still not been fully understood and successfully counteracted. In this perspective, we identified herein a single GSK3 inhibitor, CHIR99021, able to revert and avoid EnMT in primary human corneal endothelial cells (HCEnCs) from old donors until late passages in vitro (P8), as shown from cell morphology analysis (circularity). In accordance, CHIR99021 reduced expression of alpha-SMA, an EnMT marker, while restored endothelial markers such as ZO-1, Na+/K+ ATPase and N-cadherin, without increasing cell proliferation. A further analysis on RNA expression confirmed CHIR99021 induced downregulation of EnMT markers (alpha-SMA and CD44), upregulation of the proliferation repressor p21 and revealed novel insights into the beta-catenin and TGFbeta; pathways intersections in HCEnCs. The use of CHIR99021 sheds light on the mechanisms involved in EnMT and brings a substantial advantage in maintaining primary HCEnCs in culture until late passages, while preserving the correct morphology and phenotype. Altogether, these results bring crucial advancements towards the improvement of the corneal endothelial cells based therapy. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2022.10.31.514557v1?rss=1 Authors: Grinstein, S., Hirata, Y., Steinberg, B. E., Volchuk, A., matsuzawa, a., Cai, R., Freeman, S. A. Abstract: The ongoing metabolic and microbicidal pathways that support and protect cellular life generate potentially damaging reactive oxygen species (ROS). To counteract damage, cells express peroxidases, antioxidant enzymes that catalyze the reduction of oxidized biomolecules. Glutathione peroxidase 4 (GPX4) is the major hydroperoxidase specifically responsible for reducing lipid peroxides; this homeostatic mechanism is essential and its inhibition causes a unique type of lytic cell death, ferroptosis. The mechanism(s) that lead to cell lysis in ferroptosis, however, are unclear. We report that the lipid peroxides formed during ferroptosis accumulate preferentially at the plasma membrane. Oxidation of surface membrane lipids increased tension on the plasma membrane and led to the activation of Piezo1 and TRP channels. Oxidized membranes thus became permeable to cations, ultimately leading to gain of cellular Na+ and Ca2+ concomitant with loss of K+. These effects were reduced by deletion of Piezo1 and completely inhibited by blocking cation channel conductance with ruthenium red or 2-aminoethoxydiphenyl borate (2-APB). We also found that the oxidation of lipids depressed the activity of the Na+/K+-ATPase, exacerbating the dissipation of monovalent cation gradients. Preventing the changes in cation content attenuated ferroptosis. Together, our study establishes that increased membrane permeability to cations is a critical step in the execution of ferroptosis and identifies Piezo1, TRP channels and the Na+/K+-ATPase as targets/effectors of this type of cell death. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

Bu yazımızda bana her zaman komplike gelmiş bir konu olan antiaritmik ilaçları sizinle paylaşacağım. Antiaritmik ilaçlara geçmeden önce kardiyak elektrofizyolojinin üstünden çok ufak geçmemiz gerekecek ki ilaçların etki fazlarını net anlayabilelim. Konu hakkında yayımlanan Amerikan Kalp Cemiyeti derlemesi için tıklayın. Aritmi Nedir? Aritmiler acil servisin en sık başvuru sebeplerindendir. Kelime anlamı ritmin olmamasıdır ancak; kalbin hızlı, ani ya da düzensiz atışının rahatsızlık verici şekilde hissedilmesi olarak tanımlanır. Ateş, göğüs ağrısı, nefes darlığı, anksiyete, anemi ve kronik hastalıklar (hipertiroidi, kronik kalp hastalıkları, elektrolit bozuklukları,vb.) gibi nedenlerle başvuran olgularda kalp ritm bozuklukları meydana gelebilmektedir. Aritmilerin bir kısmı tamamen sağlıklı kişilerde görülebilmektedir, bu nedenle morbidite ve mortalitesi düşük olmaktadır. Bunun yanı sıra hayatı tehdit edici aritmilerle de sıkça karşılaşılmaktadır. Hastaya kesin tanıyı koyduktan sonra en uygun tedavi seçeneğine karar verilmelidir. Mevcut tıbbi imkanlarla aritmilerin büyük bir kısmının oluşumunun engellenmesi ya da oluştuktan sonra tedavisi mümkündür. Günümüzde aritmiler için birden çok tedavi alternatifi mevcuttur. Bu nedenle hekimlerin güncel kılavuzların tedavi önerilerini takip ederek uygulamaları gerekmektedir. Aritmilerin tedavisinde erken tanı konulmasının  önemi büyüktür. Aritmi tespit edilen veya aritmi şikayeti ile başvuran hastalarda ayrıntılı anamnez ve fizik muayene, çeşitli laboratuvar testleri ve 12 derivasyonlu EKG istemi yapılmalıdır. Kardiyak Temel Elektrofizyoloji Sinüs düğümünden çıkan uyarı (aksiyon potansiyeli) kalp kası kitlesi içinde belirli bir yol izleyerek yayılır. Bu yola kalbin özel ileti sistemi denir. Normal ritmik uyarıları doğuran Sinoatrial (SA) nod,Uyarıları SA noddan AV noda ileten internodal yollar, Atriyumlardan gelen uyarıların ventriküllere geçişini geciktiren Atrioventriküler (AV) nod, Uyarıları atriyumlardan ventriküllere ileten Atrioventriküler demet,Kalp uyarılarını ventriküllerin bütün bölgelerine ileten sol ve sağ Purkinje lifi demetleri. Kardiyak İleti Sistemi Kalbin özel ileti sisteminde yer alan bütün hücreler ritmik uyarılar doğurabilirler. Ancak, bu ritmik uyarıların frekansı sinüs düğümünden Purkinje sistemine doğru gidildikçe küçülür. Ritmik uyarı frekansıSinoatrial nod (SA nod)60-80 /dkAtrioventriküler nod (AV nod)40-60 /dkHis-Purkinje sistemi15-40 /dk Kardiyak iyon kanalları ve akımları: İyonlar (sodyum [Na + ], potasyum [K + ], klorür [Cl - ] ve kalsiyum [Ca 2+ ]), belirli genler tarafından kodlanan iyon kanalları ile proteinlerin oluşturduğu gözenekler ile kalp zarı kanallarından akar. Dinlenme membran potansiyeli: Dinlenme kardiyak hücre zarı potansiyeli normalde -80 ile -95 mV arasında polarizedir ve hücre içi hücre dışı boşluğa göre negatiftir. Kalpte, istirahat zar potansiyeli, istirahatte baskın açık kanal olan IK1 tarafından üretilir. Bu kanallardan akan potasyum akımı; negatif hücre içi potansiyel, potasyum için denge potansiyeli ile aynı büyüklükte olana kadar devam eder. Bu potansiyeli sürdürmek için sadece küçük miktarlarda potasyum akışı gereklidir. Sodyum ve kalsiyum için denge potansiyelleri pozitiftir (sırasıyla yaklaşık +40 mV ve yaklaşık +80 mV), dolayısıyla bu kanallar açık olduğunda membranı depolarize etme eğilimindedirler. Voltaja duyarlı sodyum, kalsiyum ve potasyum kanallarının çoğu kapalı olduğundan dinlenme durumunda küçük bir rol oynarlar. Na-K-ATPase pompası, potasyumu hücre içine ve sodyumu hücre dışına pompalayarak potasyum ve sodyum gradiyentlerini korur.  Na-Ca değiştirici, Ca'yı hücreden dışarı pompalamak için Na gradiyentinin gücünü kullanır.  Bu ve diğer pompalar, hem uyarılabilirlik hem de kasılma için önemli olan iyon kanalı gradiyentini korur. Hızlı yanıt veren dokularda aksiyon potansiyeli: Depolarizasyonu başlatmak için voltaja duyarlı,

How do β-adrenergic receptor subtypes regulate immune function in the heart? In this unique episode of The AJP-Heart and Circ Podcast, Consulting Editor Dr. Kristine DeLeon-Pennell (Medical University of South Carolina) interviews two authors about their two articles published recently in AJP-Heart and Circulatory Physiology. Dr. Laurel Grisanti (University of Missouri, Columbia) discussed her study (Tanner et al.) on the important role for β2-adrenergic receptor expression on immune cells in the development of heart failure in response to chronic catecholamine elevation. Using a chronic isoproterenol infusion model of heart failure, Dr. Grisanti and co-authors concluded that the immune cell expression of β2-adrenergic receptor is an important contributor to the detrimental responses seen with chronic elevations in catecholamine. The macrophage populations lacking β2-adrenergic receptor largely retained their reparative phenotype and failed to illicit pro-inflammatory macrophage recruitment. Dr. Petra Eder-Negrin (University Hospital, Würzburg) discussed her work (Cellini et al.) in context of Dr. Grisanti's study, underscoring the mechanistic link between sodium potassium -ATPase and β-adrenergic stimulation in the post-MI heart. Eder-Negrin and co-authors found that sodium potassium ATPase alpha 2 overexpressing cardiomyocytes are a crucial adaption, providing an important functional reserve for the heart to cope with chronic stress more efficiently. Sodium potassium ATPase alpha 2 overexpression could be an alteration to attenuate heart failure. How do these research studies connect? Listen now.   Miles A. Tanner, Charles A. Maitz, and Laurel A. Grisanti Immune cell β2-adrenergic receptors contribute to the development of heart failure Am J Physiol Heart Circ Physiol, published September 15, 2021. DOI: 10.1152/ajpheart.00243.2021   Antonella Cellini, Dorina Höfler, Paula A. Arias-Loza, Sandra Bandleon, Tanja Langsenlehner, Michael Kohlhaas, Christoph Maack, Wolfgang R. Bauer, and Petra Eder-Negrin The α2-isoform of the Na+/K+-ATPase protects against pathological remodeling and β-adrenergic desensitization after myocardial infarction Am J Physiol Heart Circ Physiol, published September 15, 2021. DOI: 10.1152/ajpheart.00808.2020

My AP Biology Thoughts  Unit 2 Cell Structure and FunctionWelcome to My AP Biology Thoughts podcast, my name is Victoria and I am your host for episode #61 called Unit 2 Cell Structure and Function: Osmotic Pressure of Animal Cells. Today we will be discussing _the osmotic pressure of animal cells. Segment 1: Introduction to Osmotic Pressure What is osmosis?  The movement of a solvent/water through a semipermeable membrane from a low concentration or high water potential, where there is less solute to a higher concentration or low water potential, and it's goal is to reach equilibrium of equal concentration of solute on the inside and out of the membrane/cell an example of passive transports as it does not require energy  What is osmotic pressure? Osmosis creates pressure  The pressure that must be applied to the solution side to stop fluid movement when a semipermeable membrane separates a solution from pure water. the pressure that would be required to stop water from diffusing through a barrier by osmosis. In other words, it refers to how hard the water would “push” to get through the barrier in order to diffuse to the other side. Determined by solute concentration, water will “try harder” to diffuse into an area with a high concentration of a solute, such as a salt, than into an area with a low concentration. Segment 2: More About Osmotic Pressure of Animal CellsWater moves to hypertonic areas It can threaten the health of cells and organisms when there is too much or too little water in the extracellular environment compared to the inside of the cell. Animal cells lack a cell wall, and use active transport systems (especially the NA+ K+ ATPase that moves 3 NA+ out for each 2 K+ that move in) to move ions outside the cell reducing the osmotic pressure.  Most protozoa use a special contractile mechanism. Water collects in a vesicle, and microfilaments force a contraction that squeezes water back outside the cell. This pump mechanism protects the cell from osmotic pressure  Segment 3: Connection to the Course How does the osmotic pressure of animals connect back to cell structure and function? Without osmotic pressure the animal cells would not be able to move solvent/water through a semipermeable membrane from a low concentration to high concentration, and not reach equilibrium of equal concentration of solute on the inside and out of the membrane/cell This will collapse its structure and both will then lead the cell to death unable to perform its necessary functions  It is vital as the cell's membrane is selective toward many of the solutes found in living organisms It determines the state/survival of the cell as well, like when it is placed in a hypotonic, isotonic, or hypertonic solutions Thank you for listening to this episode of My AP Biology Thoughts. For more student-ran podcasts and digital content, make sure that you visit http://www.hvspn.com/ (www.hvspn.com). See you next time! Music Credits:“Ice Flow” Kevin MacLeod (incompetech.com) Licensed under Creative Commons: By Attribution 4.0 License http://creativecommons.org/licenses/by/4.0/ Subscribe to our Podcasthttps://podcasts.apple.com/us/podcast/my-ap-biology-thoughts/id1549942575 (Apple Podcasts) https://open.spotify.com/show/1nH8Ft9c9f6dmo75V9imCk?si=IvI4iQV-SSaFb0ZmvTabxg (Spotify) https://podcasts.google.com/feed/aHR0cHM6Ly9mZWVkcy5jYXB0aXZhdGUuZm0vbXlhcGJpb2xvZ3l0aG91Z2h0cw (Google Podcasts  ) https://www.youtube.com/channel/UC07e_nBHLyc_nyvjF6z-DVg (YouTube)   Connect with us on Social Media·        Twitterhttps://twitter.com/thehvspn ( )https://twitter.com/thehvspn (@thehvspn)

Chapter Three: How the proximal tubule is like Elizabeth Warren and other truths my friends from Boston taught me References for Chapter 3: Faisy C, Meziani F, PLanquette B et al. Effect of Acetazolamide vs. Placebo on Duration of Invasive Mechanical Ventilation among patients with chronic obstructive pulmonary disease: a randomized clinical trial. JAMA 2016 https://pubmed.ncbi.nlm.nih.gov/26836730/This randomized controlled double blinded multi-center study of acetazolamide to shorten the duration of mechanical ventilation (known as DIABLO) there was no statistically significant difference (though it may have been underpowered to do so).Salazar H, Swanson J, Mozo K, White AC, Cabda MM Acute Mountain sickness impact among travelers to Cusco, Peru J Travel Med 2012 https://pubmed.ncbi.nlm.nih.gov/22776382/ Investigators found that altitude sickness is common and alters travel plans for 1 in 5 travelers but was prescribed infrequently.Buzas GM and Supuran CT. Journal of enzyme inhibition and medicinal chemistry 2015 https://www.tandfonline.com/doi/full/10.3109/14756366.2015.1051042This review describes the use of acetazolamide to treat peptic ulcers and how it was later learned that H. pylori have carbonic anhydrase NORDIC idiopathic intracranial Hypertension Study Writing Committee. The effect of acetazolamide on visual function in patients with idiopathic intracranial hypertension and mild visual loss: the idiopathic intracranial hypertension treatment trial. JAMA 2014 https://pubmed.ncbi.nlm.nih.gov/24756514/In this multi-centered trial, acetazolamide and low sodium weight reduction diet improved mild visual loss more than diet alone. Mullens W et al. Rationale and design of the ADVOR (acetazolamide in decompensated heart failure with volume overload trial) Eur J Heart Failure 2018 https://pubmed.ncbi.nlm.nih.gov/30238574/This reference explains the rationale for this ongoing trial.Gordon CE, Vantzelfde S and Francis JM. Acetazolamide in Lithium-induced nephrogenic diabetes insipidus NEJM 2016 https://www.nejm.org/doi/full/10.1056/NEJMc1609483A case report of efficacy of acetazolamide in a patient with severe polyuria.Zehnder D et al. Expression of 25-hydroxyvitamin D-1alpha hydroxylase in the human kidney. JASN 1999 This report explores the activity in the enzyme in nephron segments and suggests that the distal nephron may play an important part in the formation of 1,25 vitamin D https://jasn.asnjournals.org/content/10/12/2465Outline: Chapter 3 - This is chapter three, kind of the first real chapter of the book- Proximal Tubule- Reabsorbs 55-60% of the filtrate - Active sodium resorption - 65% of the sodium - 55% of the chloride - 90% of HCO3 - 100% glucose and amino acids - Passive water resorption - Water resorption is isosmotic - Secretion of - Hydrogen - Organic anions - Organic cations - Anatomy - S1, S2, S3 can be differentiated by peptidases - S1 more sodium resorption and hydrogen secretion, high capacity - S2 more organic ion secretion - Cell model - Basolateral membrane - Na-K-ATPase powers all the resorption - Luminal membrane - 100 liters a day crosses the proximal tubule cells - Microvilli to increase surface area - Microvilli has brush border which has carrier proteins as well as carbonic anhydrase - Water permeable, so sodium resorption leads to water resorption - Aquaporin-1 (sounds like this transporter is unique to the proximal tubule and RBC) - HCO3 is reabsorbed early, along with Na, resulting in increased chloride concentration which passively reabsorbed via paracellular route. - Tight junction has only one strand (on freeze fracture) as opposed to 8 in distal nephron - The Na-K-ATPase - Lower activity than in the LOH and distal nephron - Maintained intracellular Na at effective concentration of 30 mmol/L - Interior of the cell is negative due to 3 sodium out and 2 K in, then K leaks back out. - 3 Na out for 2 K in - An ATP sensitive K outflow channel on the basolateral membrane - Increased ATP slows potassium eflux - The idea is if Na-K slows, ATP will accumulate and this will slow K leaving, because there is less potassium entering. - K channel is ATP sensitive, ATP antagonizes K leak. - Highly favorable ELECTROCHEMICAL gradient for sodium to flow into the cell through the luminal membrane - Must be via a channel or carrier - Cotransporters - Amino acids - Phosphate - Glucose - Called secondary active transport - Countertransporters - Only example is H excretion - Basolateral membrane - Na-3HCO3 transporter - Powered by the negative charge in the cell- Chloride resorption - Formate chloride exchanger - Formate combines with hydrogen in the lumen, becomes neutral formic acid, and is reabsorbed where the higher pH causes it to dissociate and recycle again. - Dependent on continued H+ secretion - Chloride moves across basolateral membrane thanks to Cl and KCl transporters, taking advantage of negative intracellular charge- Passive mechanisms of proximal tubule transport - Accounts for one third of fluid resorption - Mechanism - Early proximal tubule resorts most of the bicarb and less of the chloride - Tubular fluid gets a high chloride concentration - Chloride flows through the tight junction down its concentration gradient - Sodium and water follow passively behind - Water moves osmotically into intercellular space from tubular fluid even though the osmolalities are equal since chloride is an ineffective osmole, so tonicity is not the same. ****** - Argues that bicarb is primarily important solute for passive resorbtion - Acetazolamide blocks Na and chloride resorption - Similar thing happens with metabolic acidosis where less bicarb is available to drive passive resorbtion of Na and Cl - Summary - Other than Na-K-ATPase Na-H antiporter main determinant of proximal Na and water resorption - 1. Direct bicarb resorption - Preferential bicarb resorbtion proximally drives passive chloride resorption - Drives active the formate exchanger for chloride resorption- Neurohormonal influence - AT2 drives a lot of Na resorption, primarily in S1 segment - Does not have a net effect on H-CO3 movement - Dopamine antagonizes sodium resorption - Blocks both Na-K-ATPase and - Na H antiporter- Capillary uptake - Starlings. Again - Low hydraulic pressure due to glomerular arteriole - High plasma on oncotic pressure from loss of the filtrate - The two together promote resorption - There maybe movement from interstitial back into tubular fluid (back diffusion) conflicting data- Glomerular tubular balance - The fractional tubular reabsorption remains constant despite changes in GFR (tubular load) - It is essential the GFR is matched by resorption - The rise in capillary osmotic pressure with increased GFR via increased filtration fraction is one mechanism of GT balance - Glomerular tubular balance os one of three mechanisms that prevents fluid delivery from exceeding the resorptive capacity of the tubules - GT balance - TG feedback - Autoregulation - GT balance can be altered if patients are volume overloaded or depleted - Closes this section with a story of a kid born without a brush border - Primacy of sodium in proximal tubule activity - Discusses bicarb resorbtion - There is no Tm for Bicarb as long as volume overload is prevented, in rats can rise over 60! - If you give NaHCO3 you get volume overload and the Tm I about 60 - Glucose - S1 and S2 have high capacity, low affinity glucose resorption - S3 has high affinity 2 Na fo every glucose - Tm glucose is 375 mg/min - For a GFR of 125t that comes out to 300mg/dL - 125 ml/min * 3mg/ml (300 mg/dL) = 375 mg/min - Functionally this is 200 mg/dL due to splay - Urea - Only 50-60 of filtered urea is excreted - Calcium Loop and distal tubule - Phosphate - 3Na-Phosphate high affinity transporters late in proximal tubule - three types of Na-Phos transporters, type 2 are the most important - regulated by PTH and plasma phosphate - PTH suppresses Phos resorption -Metabolic acidosis also reduces phosphate resorption (good to have phosphate in the tubule to soak up H+ - Decreased tubular pH converts HPO42- to H2PO4- which has lower affinity for phosphate binding site - Mg Loop and distal tubule - Uric AcidWhy do I love acetazolamide?- I love the proximal tubule- Many uses- Often forgottenMOA- Inhibit carbonic anhydraseMain effects- Renal: less bicarb reabsorption (ie less H secretion) à more distal Na/bicarb delivery à hypokalemic metabolic acidosis- Brain: reduce CSF production, reduce ICP/IOP, aqueous humor- Pulm: COPDNotes- Tolerance develops in 2-3 days- Sulfonamide derivative- Highly protein bound, eliminated by kidneys Source: Buzas and upuran, JEIMC, 2016S Data:1968 - High altitudeHigh altitude usually results in respiratory alkalosisAcetazolamide – lessens symptoms of altitude sickness (insomnia, headache) which occur because of periodic breathing/apnea1979- NEJM study took 9 mountaineers asleep at 5360 meters à improvement in sleep, improved SaO2 from 72 to 78.7 mmHg, reduce periodic breathing, increased alveolar ventilation (pCO2 change from 37 mmHg to 30.8mm Hg)1950s - Seizures/migrainesCAI reduces pH (more H intracellularly), K movement extracellularly à hyperpolarization and increase in seizure thresholdWeak CAI (Topamax, zonisamide) but not though to be important mechanism of antiseizure effect (topamax enhances inhibitory effect of GABA, block voltage dependent Na and Ca channels)Pulmonary/COPDThought to help with the metabolic alkalosis and as a respiratory stimulant to increase RR, TV, reduce ventilator timeIn 2001 Cochrane review – no difference in clinical outcomes, but did reduce pH and bicarb minimallyDIABLO study (RCT) on ventilated COPD patients – no difference in median duration of mechanical ventilation despite correction of metabolic alkalosisHigh altitude erythropoiesis (Monge disease)First described in 1925 via Dr. Carlos Monge Medrano (Peruvian doctor), seen in people living > 2500-3000 meters (more common in South America than other high altitude areas)Usually chronic altitude sickness with HgB > 21 g/dL + chronic hypoxemia, pHTNAcetazolamide – reduces polycythemia because induces a met acidosis à increases ventilation and arterial PPO2 and SaO2 à blunts erythropoiesis and reduces HCT and improves pulmonary vascular resistanceGI ulcersWhen H2 and PPI available, less useHistory: 1932 – observed alkaline tide, presumed existence of gastric CA (demonstrated in 1939)Acetazolamide was used to inhibit acid secretion in 1960s, ulcer symptoms, with reversible metabolic acidosis, BUT lots of SE (electrolyte losses, used Na/K/Mg salts to help, renal colic, headache, fatigue, etc)Later found H. Pylori encodes for two different CasHelps to acclimatize to acidic environmentBasically, the Ca changes CO2 into H+ and HCO3They also have a urease which produces NH3The NH3 binds with H+, leaving an alkaline environment for them to live inInhibition of CA with acetazolamide is lethal for pathogen in vitro1940sFound there was CA in pancreasThought acetazolamide to reduce volume of secretions from NGT (output from exocrine pancreas) Source: Human Anatomy at Colby Blog Diuretic resistanceIf develop hyperchloremic metabolic alkalosis, short course of acetazolamide + spironolactone (b/c need distal Na blockage) à can helpMay help with urine alkalization (ie uric acid stone) but increases risk of calcium phosphate stonesADVOR trial acetazolamide in HF exacerbation in Belgiumuse may help to prevent new episode, lower total diuretic doseCSF reduction (pseudotumor cerebri)Reduces CSF by as much as 48% when > 99.5% of CA in choroid plexus is inhibitedNORDIC trial (acetazolamide v. placebo) – improvement in visual symptoms especially if advanced papilledema, and reduced opening pressure)Side note also used off label to help with increased ICP and CSF leaks, as alternative to VP shunts, repeat LPs, etc Source: Eftekari et al, Fluid Barriers CNS, 2019.

Differences in ion concentrations inside and outside a cell cause a difference in the charge of the intracellular and extracellular environments. This electrical polarization of a cell relative to its environment is referred to as cellular membrane potential. This potential serves as an energy source for a variety of cellular functions and as a way for excitable cells like muscle cells and neurons to communicate their signals. A cell controls its membrane potential by regulating the concentration of multiple ions and other charged particles. Let's take a closer look at the biochemistry behind the cell membrane potential. After listening to this AudioBrick, you should be able to: Define equilibrium and describe the forces at work on ions across a biological membrane. Discuss the importance of the Nernst equation and equilibrium potentials. Describe the importance of Na-K-ATPase in relation to the resting membrane potential (Vr). Describe the nonequilibrium steady-state (NESS). Define and discuss the chord conductance equation. You can also check out the original brick from our Cellular Biology collection, which is available for free. Learn more about Rx Bricks by signing up for a free USMLE-Rx account: www.usmle-rx.com You will get 5 days of full access to our Rx360+ program, including nearly 800 Rx Bricks.  After the 5-day period, you will still be able to access over 150 free bricks, including the entire collections for General Microbiology and Cellular and Molecular Biology. *** If you enjoyed this episode, we'd love for you to leave a review on Apple Podcasts.  It helps with our visibility, and the more med students (or future med students) listen to the podcast, the more we can provide to the future physicians of the world. Follow USMLE-Rx at: Facebook: www.facebook.com/usmlerx Blog: www.firstaidteam.com Twitter: https://twitter.com/firstaidteam Instagram: https://www.instagram.com/firstaidteam/ YouTube: www.youtube.com/USMLERX Learn how you can access over 150 of our bricks for FREE: https://usmlerx.wpengine.com/free-bricks/

CardioNerds (Amit Goyal & Karan Desai) join University of Illinois at Chicago cardiology fellows (Brody Slostad, Kavin Arasar, and Mary Rodriguez-Ziccardi) for a cup of tea from atop Hancock Tower! They discuss an illuminating case of altered mental status & electrical instability due to digitalis poisoning. Program director Dr. Alex Auseon and APD Dr. Mayank Kansal provide the E-CPR and a message for applicants. Episode notes were developed by Johns Hopkins internal medicine resident Tommy Das with mentorship from University of Maryland cardiology fellow Karan Desai.   Jump to: Patient summary - Case media - Case teaching - References Episode graphic by Dr. Carine Hamo CardioNerds Case Reports PageCardioNerds Episode PageCardioNerds AcademyCardionerds Healy Honor RollSubscribe to our newsletter- The HeartbeatSupport our educational mission by becoming a Patron!Check out CardioNerds SWAG! Cardiology Programs Twitter Group created by Dr. Nosheen Reza Patient Summary A woman in her late 80s with history of systemic arterial hypertension and dementia presented with 2 weeks of nausea, vomiting, confusion, and yellow-tinted vision. When she presented to the hospital, initial history was limited as her caregiver was unaware of her medications and medical history. An initial ECG showed isorhythmic A-V dissociation and scooping ST segments laterally. Given her clinical history, this raised the suspicion for Digoxin toxicity, and a serum digoxin level was significantly elevated. However, this was not a home medication for the patient, nor did she have access to it! Listen to the episode now as the UIC Cardionerds masterfully take us through this case that would surely stump Dr. House!   Case Media through the Differential ABCDEFClick to Enlarge A. Initial ECGB. CXR- Patchy opacities of the left lower lobe consistent with pulmonary edema and/or aspiration​ pneumonia.C. Repeat ECG: AF with AV block, persistent scooped T waves​D. Post arrest ECG: Flutter/fib with AV block, VERY LONG PAUSES up to 6 secondsE. ECG post TVP: A flutter, slow V response (pacing picking up), intrinsic ventricular rate 20-40, PM set to 50 bpmF. Most recent ECG: Normal sinus rhythm TTE Episode Schematics & Teaching The CardioNerds 5! – 5 major takeaways from the #CNCR case 1) This episode featured a challenging case of digitalis toxicity. Cardionerds, what is the mechanism of action of cardiac glycosides?   Cardiac Glycosides (such as digoxin, digitalis, and oubain), inhibit the myocardial Na/K ATPase pump. This leads to an increased concentration of intracellular sodium, which then drives the influx of calcium into cardiac myocytes via the Na/Ca exchanger. This increase in intracellular calcium leads to further calcium release from the sarcoplasmic reticulum making even more calcium available to bind to troponin, increasing contractility. In addition to their effect on inotropy, cardiac glycosides increase vagal tone, reducing SA node activity and slowing conduction through the AV node by increasing the refractory period  2) The first published account of digitalis to treat heart failure dates back to the 18th century, when botanist and physician William Withering published "An account of the Foxglove and some of its medical uses with practical remarks on dropsy, and other diseases". A lot has changed over the years; what are some of the uses of digoxin in the modern day?   The DIG trial (1997) demonstrated a reduction in hospitalizations in patients with HFrEF treated with digoxin. However, no impact on mortality was shown. A major limitation from randomized trials of digoxin is the lack of contemporary background HF treatment (e.g., ARNI, SGLT2i, MRA, Device Therapy). Thus, its role in modern HFrEF management is typically limited to reducing hospitalizations in patients with persistent NYHA Class III or IV symptoms despite maximally tolerated guideline-directed medical therapy Digoxi...

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.11.09.373902v1?rss=1 Authors: Ladefoged, L. K., Schiott, B., Fedosova, N. U. Abstract: Kinetic properties and crystal structures of the Na+,K+-ATPase in complex with cardiotonic steroids (CTS) revealed significant differences between CTS subfamilies (Laursen et al., 2015): beneficial effects of K+ on bufadienolide binding strongly contrasted with K+/cardenolide antagonism. To solve this riddle we applied docking and molecular dynamics simulations of the complexes involving Na+,K+-ATPase, bufadienolides (bufalin, cinobufagin), and ions (K+, Na+, Mg2+). The results revealed that bufadienolide binding is affected by i) electrostatic attraction of the lactone ring by a cation, and ii) the ability of a cation to stabilize and ''shape'' the site constituted by transmembrane helices of the -subunit (M1-6). The latter effect was due to varying coordination patterns involving amino acid residues from helix bundles M1-4 and M5-10. Substituents on the steroid core of a bufadienolide add to and modify the cation effects. The above rationale is fully consistent with the ion effects on the kinetics of Na+,K+-ATPase/bufadienolide interactions. Copy rights belong to original authors. Visit the link for more info

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.10.03.319137v1?rss=1 Authors: Smith, R. S., Florio, M., Akula, S., Neil, J., Wang, Y., Hill, R. S., Goldman, M., Mullally, C., Reed, N., Bello-Espinosa, L., Sarnat, L. F., Monteiro, F., Erasmo, C., Pinto e Vairo, F., Morava, E., Barkovich, A. J., Gonzalez-Heydrich, J., Brownstein, C., McCarroll, S., Walsh, C. A. Abstract: Osmotic equilibrium and membrane potential in animal cells depend on concentration gradients of sodium (Na+) and potassium (K+) ions across the plasma membrane, a function that is catalyzed by the Na,K-ATPase 3 subunit. In vertebrates, four paralogous genes, ATP1A1-4, encode distinct alpha subunit isoforms ( 1- 4), three of which ( 1, 2, 3; are expressed in the brain, and two ( 1, 3) predominantly in neurons. The 3 isoform, encoded by ATP1A3, is critical to neuronal physiology, and a growing spectrum of neurological diseases are associated with ATP1A3 pathogenic variants, with ages of onset ranging from early childhood to adulthood. Here, we describe ATP1A3 variants encoding dysfunctional 3 subunits in children affected by polymicrogyria, a developmental malformation of the cerebral cortex characterized by abnormal folding and laminar organization. To gain cell-biological insights into the spatiotemporal dynamics of prenatal ATP1A3 expression, we established a transcriptional atlas of ATP1A3 expression during cortical development using mRNA in situ hybridization and transcriptomic profiling of ~125,000 individual cells with single-cell RNA sequencing (Drop-Seq) from various areas of the midgestational human neocortex. We find that fetal expression of ATP1A3 is restricted to a subset of excitatory neurons carrying transcriptional signatures of neuronal activity and maturation characteristic of the developing subplate. Furthermore, by performing Drop-Seq on ~52,000 nuclei from four different areas of an infant human neocortex, we show that ATP1A3 expression persists throughout early postnatal development, not only within excitatory neurons across all cortical layers, but also and more predominantly in inhibitory neurons, with specific enrichment in fast-spiking basket cells. In addition, we show that ATP1A3 expression, both in fetal and postnatal neurons, tends to be higher in frontal cortical areas than in occipital areas, in a pattern consistent with the rostro-caudal maturation gradient of the human neocortex. Finally, we discover distinct co-expression patterns linking catalytic and {beta} ; subunit isoforms (ATP1A1,2,3) and auxiliary isoforms (ATP1B1,2,3), suggesting the ATPase pump may form non-redundant, cell-type specific alpha-beta combinations. Together, the importance of the developmental phenotypes and dynamic expression patterns of ATP1A3 point to a key role for 3 in the development and function of human cortex. Copy rights belong to original authors. Visit the link for more info

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.09.08.288266v1?rss=1 Authors: Sharples, S. A., Vargas, A., Lognon, A. P., Young, L., Shonak, A., Cymbalyuk, G. S., Whelan, P. J. Abstract: Developing spinal motor networks produce a diverse array of outputs, including episodic and continuous patterns of rhythmic activity. Variation in excitability state and neuromodulatory tone can facilitate transitions between episodic and continuous rhythms; however, the intrinsic mechanisms that govern these rhythms and transitions are poorly understood. Here, we tested the capacity of a single central pattern generator (CPG) circuit with tunable properties to generate multiple outputs. To address this, we deployed a computational model composed of an inhibitory half-centre oscillator. We tested the contributions of key properties predicted by the model to the generation of an episodic rhythm produced by isolated spinal cords of the newborn mouse. The model was capable of reproducing the diverse state-dependent rhythms evoked by dopamine in the neonatal mouse spinal cord. In the model, episodic bursting depended predominantly on the endogenous oscillatory properties of neurons, with persistent Na+(INaP), Na+-K+ ATPase pump (IPump), and hyperpolarization-activated currents (Ih) playing key roles. Modulation of all three currents produced transitions between episodic and continuous rhythms and silence. Pharmacological manipulation of these properties in vitro led to consistent changes in spinally generated rhythmic outputs elicited by dopamine. The model also showed multistable zones within a narrow range of parameter space for IPump and Ih, where switches between rhythms were rapidly triggered by brief but specific perturbations. Outside of those zones, brief perturbations could reset episodic and continuous rhythmicity generated by the model. Our modelling and experimental results provide insight into mechanisms that govern the generation of multiple patterns of rhythmicity by a single CPG. We propose that neuromodulators alter circuit properties to position the network within regions of state-space that favour stable outputs or, in the case of multistable zones, facilitate rapid transitions between states. Copy rights belong to original authors. Visit the link for more info

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.06.12.148437v1?rss=1 Authors: Jolivet, R. B., Magistretti, P. J. Abstract: Spike-frequency adaptation is a prominent feature of spiking neurons. Using a Hodgkin-Huxley-type model, we studied adaptation originating from the Na,K-ATPase electrogenic pump and its evolution in presence of a medium-duration calcium-dependent potassium channel. We found that the Na,K-ATPase induces spike-frequency adaptation with a time constant of up to a few seconds and interacts with the calcium-dependent potassium current through the output frequency, yielding a very typical pattern of instantaneous frequencies. Because channels responsible for spike-frequency adaptation can interact with each other, our results suggest that their meaningful time courses and parameters can be difficult to measure experimentally. To circumvent this problem, we developed a simple phenomenological model that captures the interaction between currents and allows the direct evaluation of the underlying biophysical parameters directly from the frequency vs. current curves. Finally, we found that for weak stimulations, the pump induces phasic spiking and linearly converts the stimulus amplitude in a finite number of spikes acting like an inhibitory spike-counter. Our results point to the importance of considering interacting currents involved in spike-frequency adaptation collectively rather than as isolated elements and underscore the importance of sodium as a messenger for long-term signal integration in neurons. Within this context, we propose that the Na,K-ATPase plays an important role and show how to recover relevant biological parameters from adapting channels using simple electrophysiological measurements. Copy rights belong to original authors. Visit the link for more info

Your body isn’t strung with copper wire. So how does the nervous system send electrical signals? Libby and Ruka discuss this question and attempt to do math. When you’re done listening, remember to write that letter to your Nana Amps. She misses you. Key Words action potential, axon terminal, axon, cell membrane, current, electrical potential, excitatory, extracellular, gap junction, graded potential, inhibitory, intracellular, ions, leak channels, megaohms (mΩ), membrane potential, millivolts (mV), myelin, Na+/K+-ATPase, nanoamps (nA), negative charge, Ohm’s law, pacemaker potential, permeability, positive charge, potential difference, potential, propagation, receptor potential, resistance, resting membrane potential, signal transduction, synaptic potential, threshold, transmembrane potential, V=IR, volts   Old West Words of the Day John B. John Barleycorn Brother Jonathan   Connect with us! FB @HeadshakeShow T @HeadshakeShow ‘Sta @HeadshakeNinja Site headshake.show OR headshake.ninja   References Textbooks Principles of Neural Science, Kandel, Schwartz, and Jessell, 4th Edition Vander’s Human Physiology, 13th Edition   Music Bushwick Tarantella by Kevin MacLeod is licensed under a Creative Commons Attribution license (https://creativecommons.org/licenses/by/4.0/) Source: http://incompetech.com/music/royalty-free/index.html?isrc=USUAN1300002 Artist: http://incompetech.com/ Modified from original with volume fading and cuts   Disclaimer This podcast is for entertainment and education only. Neither of the hosts is a medical doctor, and nothing they say is medical advice. Please consult with your physician before making decisions about your health.

How metabolic Acidosis causes Hyperkalemia. H+ enters all cells including Principal cells. K+ leaves principal cells and enters blood. Leading to Hyperkalemia. High K+ level is maintained by decreasing Na+—K+ ATPase and K+ channel activities. --- Support this podcast: https://anchor.fm/kamesa-anota/support

Generally speaking, toads are laid back, easy-going creatures. But every so often a species will find itself an invader in a new land and wreak total havoc. We discuss one such toad (but not necessarily the one you might think). Of course there is a toad which is brand new to science as well, in our Species of the Bi-Week. FULL REFERENCE LIST AVAILABLE AT: herphighlights.podbean.com  Main Paper References: Moore, M, JFSN Fidy, and D Edmonds. 2015. “The New Toad in Town: Distribution of the Asian Toad, Duttaphrynus Melanostictus, in the Toamasina Area of Eastern Madagascar.” Tropical Conservation Science 8 (2): 440–55. Marshall, BM, NR Casewell, M Vences, F Glaw, F Andreone, A Rakotoarison, G Zancolli, F Woog, and W Wüster. 2018. “Widespread Vulnerability of Malagasy Predators to the Toxins of an Introduced Toad.” Current Biology 28 (11): R654–55. Species of the Bi-Week: Landestoy T., MA, DB Turner, AB Marion, and SB Hedges. 2018. “A New Species of Caribbean Toad (Bufonidae, Peltophryne) from Southern Hispaniola.” Zootaxa 4403 (3): 523. Other Mentioned Papers/Studies: Brown, GP, BL Phillips, JK Webb, and R Shine. 2006. “Toad on the Road: Use of Roads as Dispersal Corridors by Cane Toads (Bufo marinus) at an Invasion Front in Tropical Australia.” Biological Conservation 133 (1): 88–94. Feit, B, CE Gordon, JK Webb, TS Jessop, SW Laffan, T Dempster, and M Letnic. 2018. “Invasive Cane Toads Might Initiate Cascades of Direct and Indirect Effects in a Terrestrial Ecosystem.” Biological Invasions. Springer International Publishing, 1–15. Jenkins, RKB, A Rabearivelo, CT Chan, WM Andre, R Randrianavelona, and JC Randrianantoandro. 2009. “The Harvest of Endemic Amphibians for Food in Eastern Madagascar.” Tropical Conservation Science 2 (1): 25–33. Kelly, E, and BL Phillips. 2018. “Targeted Gene Flow and Rapid Adaptation in an Endangered Marsupial.” Conservation Biology, June. Kuo, H-Y, C-W Hsu, J-H Chen, Y-L Wu, and Y-S Shen. 2007. “Life-Threatening Episode after Ingestion of Toad Eggs: A Case Report with Literature Review.” Emergancy Medecine Journal 24 (3): 215–16. Llewelyn, J, K Bell, L Schwarzkopf, RA Alford, and R Shine. 2012. “Ontogenetic Shifts in a Prey’s Chemical Defences Influence Feeding Responses of a Snake Predator.” Oecologia 169 (4): 965–73. O’Shea, M, A Kathriner, S Mecke, C Sanchez, and H Kaiser. 2013. “‘Fantastic Voyage’: A Live Blindsnake (Ramphotyphlops Braminus) Journeys through the Gastrointestinal System of a Toad (Duttaphrynus melanostictus).” Herpetology Notes 6 (1): 467–70. Mohammadi, S, Z Gompert, J Gonzalez, H Takeuchi, A Mori, and AH Savitzky. 2016. “Toxin-Resistant Isoforms of Na+/K+-ATPase in Snakes Do Not Closely Track Dietary Specialization on Toads.” Proceedings of the Royal Society B: Biological Sciences 283: 20162111. Phillips, BL, and R Shine. 2004. “Adapting to an Invasive Species: Toxic Cane Toads Induce Morphological Change in Australian Snakes.” Proceedings of the National Academy of Sciences of the United States of America 101 (49): 17150–55. Pramuk, JB, T Robertson, JW Sites, and BP Noonan. 2008. “Around the World in 10 Million Years: Biogeography of the Nearly Cosmopolitan True Toads (Anura: Bufonidae).” Global Ecology and Biogeography 17 (1): 72–83. Reardon, J. T., Kraus, F., Moore, M., Rabenantenaina, L., Rabinivo, A., Rakotoarisoa, N. H., & Randrianasolo, H. H. (2018). Testing tools for eradicating the invasive toad Duttaphrynus melanostictus in Madagascar. Conservation Evidence 15, 12-19. Ujvari, B, HC Mun, AD Conigrave, A Bray, J Osterkamp, P Halling, and T Madsen. 2013. “Isolation Breeds Naivety: Island Living Robs Australian Varanid Lizards of Toad-Toxin Immunity via Four-Base-Pair Mutation.” Evolution 67 (1): 289–94. Ujvari, B, H Mun, AD Conigrave, C Ciofi, and T Madsen. 2014. “Invasive Toxic Prey May Imperil the Survival of an Iconic Giant Lizard, the Komodo Dragon.” Pacific Conservation Biology 20 (4): 363–65. Ujvari, B, NR Casewell, K Sunagar, K Arbuckle, W Wüster, N Lo, D O’Meally, et al. 2015. “Widespread Convergence in Toxin Resistance by Predictable Molecular Evolution.” Proceedings of the National Academy of Sciences 112 (38): 11911–11916. Vences, M, JL Brown, A Lathrop, GM Rosa, A Cameron, A Crottini, R Dolch, et al. 2017. “Tracing a Toad Invasion: Lack of Mitochondrial DNA Variation, Haplotype Origins, and Potential Distribution of Introduced Duttaphrynus melanostictus in Madagascar.” Amphibia-Reptilia 38 (2): 197–207. Wogan, GOU, BL Stuart, DT Iskandar, and JA McGuire. 2016. “Deep Genetic Structure and Ecological Divergence in a Widespread Human Commensal Toad.” Biology Letters 12 (1): 20150807. Other Links/Mentions: CrocFest - www.crocfest.org Music: Intro/outro – Treehouse by Ed Nelson Other Music – The Passion HiFi, www.thepassionhifi.com

We back for another invertebrate versus amphibian episode. But this time we’re focusing on carabid beetles and their relentless consumption all amphibian life. They have managed to turn the tables on their would be predator in a remarkable case of role-reversal. Species of the Bi-week is a beautiful frog with a fittingly macabre name. FULL REFERENCE LIST AVAILABLE AT: herphighlights.podbean.com Main Paper References: Wizen, G., and A. Gasith. 2011. “Predation of amphibians by carabid beetles of the genus Epomis found in the central coastal plain of Israel.” Zookeys 100: 181–191. Wizen, G., and A. Gasith. 2011. “An unprecedented role reversal: Ground beetle larvae (Coleoptera: Carabidae) lure amphibians and prey upon them.” PLoS One 6: 1–6. Species of the Bi-Week: Dias, I. R., C. F. B. Haddad, A. J. S. Argôlo, and V. G. D. Orrico. 2017. “The 100th: An appealing new species of Dendropsophus (Amphibia: Anura: Hylidae) from northeastern Brazil R. Castiglia.” PLoS One 12: e0171678. Other Mentioned Papers/Studies: Barkai A, McQuaid C (1988) Predator–prey role reversal in marine benthic ecosystems. Science 242: 62–64. Beckmann, C, and R Shine. 2011. “Toad’s Tongue for Breakfast: Exploitation of a Novel Prey Type, the Invasive Cane Toad, by Scavenging Raptors in Tropical Australia.” Biological Invasions 13 (6): 1447–55. Brodie Jr., ED. 1977. “Hedgehogs Use Toad Venom in Their Own Defence.” Nature 268 (5621): 627–28. Choh, Y., Takabayashi, J., Sabelis, M. W., & Janssen, A. (2014). Witnessing predation can affect strength of counterattack in phytoseiids with ontogenetic predator–prey role reversal. Animal Behaviour, 93, 9-13. Escoriza, D., L. Mestre, G. Pascual, and J. Buse. 2017. “First case of attack of an adult Bufo spinosus Daudin, 1803 by a carabid beetle larva of Epomis circumscriptus (Duftschmid, 1812).” Bol. Asoc. Herpetol. Esp. 28: 2006–2008. Petschenka, G, S Fandrich, N Sander, V Wagschal, M Boppré, and S Dobler. 2013. “Stepwise Evolution of Resistance to Toxic Cardenolides via Genetic Substitutions in the Na+/K+-ATPase of Milkweed Butterflies (Lepidoptera: Danaini).” Evolution 67 (9): 2753–61. Scudder, GGE, and J Meredith. 1982. “The Permeability of the Midgut of Three Insects to Cardiac Glycosides.” Journal of Insect Physiology 28 (8): 689–94. Ujvari, B, NR Casewell, K Sunagar, K Arbuckle, W Wüster, N Lo, D O’Meally, et al. 2015. “Widespread Convergence in Toxin Resistance by Predictable Molecular Evolution.” Proceedings of the National Academy of Sciences 112 (38): 11911–11916. Wilson, NJ, AN Stokes, GR Hopkins, ED Brodie, Jr., and CR Williams. 2014. “Functional and Physiological Resistance of Crayfish to Amphibian Toxins: Tetrodotoxin Resistance in the White River Crayfish (Procambarus Acutus).” Canadian Journal of Zoology 92 (11): 939–45. Voyles, J, DC Woodhams, V Saenz, AQ Byrne, R Perez, G Rios-sotelo, MJ Ryan, et al. 2018. “Shifts in Disease Dynamics in a Tropical Amphibian Assemblage Are Not due to Pathogen Attenuation.” Science 359: 1517–19. Other Links/Mentions: Epomis circumscriptus attacking and preying upon Bufo viridis – http://www.youtube.com/watch?v=wFJ_CXJ0qPo Epomis circumscriptus attacking and preying upon Hyla savignyi – http://www.youtube.com/watch?v=RMkFb5n97cU Trophic interactions between Epomis adults and Triturus vittatus –  http://www.youtube.com/watch?v=JA46dbEpluI Videos from Wizen and Gasith 2011 PLoS One  – http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0025161 Photos from paper two: http://www.tau.ac.il/lifesci/departments/zoology/Amphibia/new.html Rats vs toads: https://www.facebook.com/groups/ukargs/permalink/2092225931007478/ Music: Intro/outro – Treehouse by Ed Nelson Other Music – The Passion HiFi, www.thepassionhifi.com

Roy Silverstein explains how the Na+/K+-ATPase helps turn macrophages into foam cells at atherosclerotic plaques.

Sodium chloride transport across isolated cecum mucosa was investigated in normal rats and rats with adaptive cecum growth induced by dietary polyethylene glycol (PEG). The normal cecum absorbed CI in excess of Na with a small short-circuit current (Isc). Dietary adaptation led to large equivalent increments of Na and Cl net absorption without adequate Ise change. Inhibitor studies (mucosal amiloride 10(-3) and 10(-4) M; mucosal 4,4-diisolhiocyanatostilbene-2,2-disulfonic acid 5 x 10(-5) M;serosal furosemide 10(-3) M;serosal ouabain 10(-3) M) suggested that normal cecal NaCl absorption involves electroneutral Na/N and Cl/HCO3 exchange at the apical and Na-K-ATPase-mediated exit across the basolateral cell membrane. Dietary adaptation stimulates the loosely coupled antiports and possibly activates a small serosally located NaCl cotransport. Comparative histology showed flattening of all tissue layers and widening of crypts in PEG animals. Crypt widening may facilitate ion access to underutilized transport sites and, at least in part, explain the increased absorption of the enlarged cecum.

The compensatory hypertrophy in different renal cortical structures was studied in rats 10 and 21 days after unilateral nephrectomy (UNX). Quantitative morphological/stereological analysis revealed significant increases in total renal cortical volume - 33% on day 10 and 48% on day 21 - after UNX. These changes were paralleled by significant increments in the volumes of proximal convoluted tubule (PCT, 55%), distal convoluted tubule (DCT, 114%), and cortical collecting duct (CCD, 106%) segments on day 10. The corresponding changes on day 21 were 76, 122, and 212%, respectively. These alterations were accompanied by increases in segment length; 3% PCT, 23% DCT, and 50% CCD on day 10 and 9% PCT, 30% DCT, and 142% CCD on day 21 after UNX. The total luminal and basolateral cell membrane surface areas also exhibited a time-dependent increase after UNX. The increments in both luminal and basolateral membrane domains in PCT and DCT after 10 days were not significant, but reached significance after 21 days (PCT: luminal membrane 21%, basolateral membrane 63%; DCT: luminal membrane 98%, basolateral membrane 63%). In contrast, CCD membrane areas had increased substantially already 10 days after UNX (luminal membrane 92%, basolateral membrane 71%). It declined subsequently by day 21 (luminal membrane 57%, basolateral membrane 32%). The cell rubidium concentration after a 30-second rubidium infusion, an index of Na-K-ATPase activity, as well as sodium concentrations were unaltered in cells of all nephron segments investigated. Altogether the stereological analysis shows that the compensatory increase in organ volume can be attributed primarily to an increase in nephron epithelial volume. The PCT responds with `radial' hypertrophy (thickening of the tubular epithelial wall), while the DCT undergoes `length' hypertrophy (increase of tubular length without thickening of the tubular wall and without an increase in number of cells). This type of hypertrophy is especially prominent on day 21 after UNX for the CCD which doubles in length. Only on day 10 does the CCD seem to respond with hyperplasia. Adaptive changes in response to UNX develop gradually. Only a few of the morphological parameters studied had completed their change by 10 days, the majority required longer.

Purified secretory vesicles isolated from bovine neurohypophyses take up Na+ under the same circumstances where an efflux of Ca2+ takes place, suggesting a Na+/Ca2+ exchange. Potassium cannot substitute for Na+ in this process. Also, a Ca2+/Ca2+ exchange can occur. Inhibiting the latter process by Mg2+ allowed to estimate an apparent KM of 0.7 μM free Ca2+ and a maximal uptake of 1.5 nmol × mg protein−1 × min−1 Ca2+ in exchange for Na+. The vesicles did not contain plasma membrane marker (Na+/K+ ATPase) as shown by distribution analyses on the density gradients on which they were purified. Similarly, distribution studies also showed that no other ATPase activity could be detected in the purified vesicle fraction. It is concluded that a Na+/Ca2+ exchange is operating across the secretory vesicle membrane and that it is not directly dependent on ATP hydrolysis.