Podcasts about na ca2

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2023.07.16.549200v1?rss=1 Authors: Yan, J., Lan, W., Yang, Q., Yang, Q., He, X., Dong, Y., Hu, Z., Jiao, K., Paquet-Durand, F. Abstract: Inherited retinal degeneration (IRD) refers to a group of untreatable blinding diseases characterized by a progressive loss of photoreceptors. IRD pathology is often linked to an excessive activation of cyclic nucleotide-gated channels (CNGC) leading to Na+- and Ca2+-influx, subsequent activation of voltage-gated Ca2+-channels (VGCC), and further Ca2+ influx. However, whether and how exactly intracellular Ca2+ overload contributes to photoreceptor degeneration is still controversial. Here, we used whole-retina and single-cell RNA-sequencing to compare gene expression between the rd1 mouse model for IRD and wild-type (wt) mice. Differentially expressed genes were linked to several Ca2+-signalling related pathways. To explore this further, organotypic retinal explant cultures derived from rd1 and wt mice were treated with the intracellular Ca2+-chelator BAPTA-AM and with inhibitors for different Ca2+-permeable channels, including CNGC, L-type VGCC, T-type VGCC, Ca2+-release-activated channel (CRAC), and Na+/Ca2+ exchanger (NCX). Moreover, we employed the compound NA-184 to selectively inhibit the Ca2+-dependent protease calpain-2. The overall activity of poly(ADP-ribose) polymerases (PARPs), sirtuin-type histone-deacetylases, calpains, as well as the activation of calpain-1, and -2 were analysed in situ on retinal tissue sections. Cell viability was assessed via the TUNEL assay. While rd1 photoreceptor cell death was reduced by BAPTA-AM, the effects of Ca2+-channel blockers were ambiguous, with T-type VGCC and NCX inhibition showing protection, while blocking CNGC and CRAC was detrimental. Activity of calpains and PARPs generally followed similar trends as cell death. Remarkably, sirtuin activity and calpain-1 activation was associated with photoreceptor protection, while calpain-2 activity was linked to degeneration. Accordingly, the calpain-2 inhibitor NA-184 protected rd1 photoreceptors. Together, these results indicate that Ca2+ overload in rd1 photoreceptors may be triggered by T-type VGCC in conjunction with NCX. High Ca2+-levels likely suppress the protective activity of calpain-1 and promote neurodegeneration via activation of calpain-2. Our study details the complexity of Ca2+-signalling in photoreceptors and emphasizes the importance of identifying and targeting degenerative processes to achieve a therapeutic benefit for IRD. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

In episode 53 of the pharmaceutical calculations podcast, you will learn how to calculate the mEq/L of Na+, Ca2+ and Cl- in a fluid having 0.25M NaCl and 0.075 CaCl2. Key equations and pertinent concepts are also reviewed. This episode was originally broadcast as a video on our YouTube channel: www.youtube.com/pharmaceuticalcalculationseasy Additional Resources for Practice: Pharmaceutical Calculations: 1001 Questions with Answers: https://www.rxcalculations.com/shop/uncategorized/pharmaceutical-calculations-1001-questions-answers/ NAPLEX Question Bank: https://www.rxcalculations.com/shop/uncategorized/gold-membership/ Join Our Social Media Community: Website: http://www.rxcalculations.com Forum: https://forum.rxcalculations.com/ Facebook: https://www.facebook.com/pharmaceuticalcalculations Twitter: https://twitter.com/RxCalculations Instagram: https://www.instagram.com/rxcalculations YouTube: www.youtube.com/pharmaceuticalcalculationseasy About RxCalculations: RxCalculations helps you master pharmaceutical calculations. We make it so you never have to worry about failing an exam or compromising patient safety because of a calculations error. RxCalculations is a leading global educational service platform focused on developing top quality pharmaceutical calculations products to help prospective pharmacists and health care professionals all over the world resolve one of the biggest challenges related to their profession. Our top quality products include affordable courses, personal consults, books, video tutorials, timed quizzes and apps designed to make you an expert in solving any pharmaceutical calculations question. We also have the largest pharmaceutical calculations online question bank which has over 1000 questions covering every important calculations topic as well as step-by-step video solutions. With all these resources at your disposal we have all you need to not only master pharmacy calculations but ace every test as well as passing your board exams.

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.10.19.345579v1?rss=1 Authors: Hjukse, J. B., Vindedal, G. F., Sprengel, R., Jensen, V., Nagelhus, E. A., Tang, W. Abstract: Astrocytes are intricately involved in the activity of neural circuits, however, their basic physiology of interacting with neurons remains controversial. Using dual-indicator two-photon imaging of neurons and astrocytes during stimulations of hippocampal CA3 - CA1 Schaffer collateral (Scc) excitatory synapses, we report that under physiological conditions, the increased glutamate released from the higher frequency stimulation of neurons can accelerate local astrocytic Ca2+ levels. As consequences of extracellular glutamate clearance and maintaining of astrocytic intracellular Na+ homeostasis, the increase of astrocytic membrane Ca2+ permeability via Na+/Ca2+ exchanger (NCX) reverse mode is the primary reason of eliciting astrocytic intracellular Ca2+ elevation upon neuronal stimulation. This Ca2+-induced Ca2+ release is dependent on inositol triphosphate receptor type 2 (IP3R2). In addition, ATP released from Scc excitatory synapses can contribute to this molecular mechanism of Ca2+-induced Ca2+ release in astrocytes. Copy rights belong to original authors. Visit the link for more info

Coated microvesicles isolated from bovine neurohypophyses could be loaded with Ca2+ in two different ways, either by incubation in the presence of ATP or by imposition of an outwardly directed Na+ gradient. Na+, but not K+, was able to release Ca2+ accumulated by the coated microvesicles. These results suggest the existence of an ATP-dependent Ca2+-transport system as well as of a Na+/Ca2+ carrier in the membrane of coated microvesicles similar to that present in the membranes of secretory vesicles from the neurohypophysis. A kinetic analysis of transport indicates that the apparent Km for free Ca2+ of the ATP-dependent uptake was 0.8 microM. The average Vmax. was 2 nmol of Ca2+/5 min per mg of protein. The total capacity of microvesicles for Ca2+ uptake was 3.7 nmol/mg of protein. Both nifedipine (10 microM) and NH4Cl (50 mM) inhibited Ca2+ uptake. The ATPase activity in purified coated-microvesicles fractions from brain and neurohypophysis was characterized. Micromolar concentrations of Ca2+ in the presence of millimolar concentrations of Mg2+ did not change enzyme activity. Ionophores increasing the proton permeability across membranes activated the ATPase activity in preparations of coated microvesicles from brain as well as from the neurohypophysis. Thus the enzyme exhibits properties of a proton-transporting ATPase. This enzyme seems to be linked to the ion accumulation by coated microvesicles, although the precise coupling of the proton transport to Ca2+ and Na+ fluxes remains to be determined.

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.

Abstract: Bovine chromaffin secretory vesicle ghosts loaded with Na+ were found to take up Ca2+ when incubated in K+ media or in sucrose media containing micromolar concentrations of free Ca2+. Li+- or choline+loaded ghosts did not take up Ca2+. The Ca2+ accumulated by Na+-loaded ghosts could be released by the Ca2+ ionophore A23187, but not by EGTA. Ca2+ uptake was inhibited by external Sr2+, Na +, Li +, or choline +. All the 45Ca2+ accumulated by Na+-dependent Ca2+ uptake could be released by external Na +, indicating that both Ca2+ influx and efflux occur in a Na+-dependent manner. Na + -dependent Ca2+ uptake and release were only slightly inhibited by Mg2+. In the presence of the Na+ ionophore Monensin the Ca2+ uptake by Na +-loaded ghosts was reduced. Ca2+ sequestered by the Na+-dependent mechanism could also be released by external Ca2+ or Sr2+ but not by Mg2+, indicating the presence of a Ca2+/Ca2+ exchange activity in secretory membrane vesicles. This Ca2+/Ca2+ exchange system is inhibited by Mg2+, but not by Sr2+. The Na + -dependent Ca2+ uptake system in the presence of Mg2+ is a saturable process with an apparent Km of 0.28 μM and a Vmax= 14.5 nmol min−1 mg protein−1. Ruthenium red inhibited neither the Na+/Ca2+ nor the Ca2+/Ca2+ exchange, even at high concentrations.

Intact secretory vesicles isolated from bovine adrenal medulla contain 94 nmol Na+ per mg of protein, and Ca2+ influx into the vesicles is inhibited by increasing concentrations of extravesicular Na+ (but not of K+, Li+ or choline+) or by addition of the Na+ ionophore monensin. Thus Ca2+ influx is determined by the Na+ gradient across the vesicular membrane. Half maximal inhibition of Ca2+ influx occurs with 34 mM Na+ extravesicularly. The fact that Ca2+ can also be released from the vesicles by inversion of the Na+ gradient provides direct evidence that an Na+-Ca2+ exchange may operate. According to an analysis of the inhibition of Ca2+ uptake by Na+ in a Hill plot 2 Na+ would be exchanged for 1 Ca2+. Ca2+ influx into the vesicles increases with temperature (energy of activation: 16 kcal/mol), can be observed already with 10−7 M free Ca2+ and increases up to 10−4 M Ca2+. Ca2+ influx is not affected by Mg2+ but Sr2+ is inhibitory. Since the process is only slightly influenced by the pH of the incubation medium and is insensitive to Mg2+-ATP or inhibitors of the proton translocating Mg2+-ATPase the electrochemical proton gradient across the vesicular membrane does not affect directly the Ca2+ influx into the secretory vesicles. Ca2+ uptake is insensitive to ruthenium red and oligomycin.