Mineralocorticoid Receptor in Calcium Handling of Vascular Smooth Muscle Cells

For decades, the mineralocorticoid receptor (MR) antagonists have been used for the management of cardiovascular diseases; however, the molecular mechanisms involved in their beneficial effects are not fully understood. Recent publications point to the fundamental role of aldosterone and vascular MR in the regulation of arterial tone, vascular contractility, and cell proliferation. However, the intricate transduction machinery activated by vascular MRs has begun to be revealed with the help of transgenic rodent models and novel transcriptional analysis approaches. Specifically, in this chapter, we review and discuss the most recent contributions about the fine-tuning that the MR exerts on the expression and function of ion channels that participate in calcium handling of vascular cells and the therapeutic implications for hypertension and cardiovascular diseases

Agrárpiaci Jelentések, Baromfi

Amerikai Egyesült Államok agrárminisztériumának (USDA) májusban megjelent jelentése szerint az USA csirkehústermelése 4,6 millió tonna körül alakult 2017 első negyedévében, ami 2 százalékkal haladta meg az előző év azonos időszakának kibocsátását. Az Európai Bizottság adatai alapján 2017 első 20 hetében 178 euró/100 kilogramm volt az egész csirke uniós átlagára, kismértékben csökkent az előző év hasonló időszakának átlagárához viszonyítva. Magyarországon a vágócsirke élősúlyos termelői ára (245,9 forint/kilogramm) 4,3 százalékkal volt alacsonyabb 2017 20. hetében az egy évvel korábbinál

RyRCa2+ Leak Limits Cardiac Ca2+ Window Current Overcoming the Tonic Effect of Calmodulin in Mice

Ca2+ mediates the functional coupling between L-type Ca2+ channel (LTCC) and sarcoplasmic reticulum (SR) Ca2+ release channel (ryanodine receptor, RyR), participating in key pathophysiological processes. This crosstalk manifests as the orthograde Ca2+-induced Ca2+-release (CICR) mechanism triggered by Ca2+ influx, but also as the retrograde Ca2+-dependent inactivation (CDI) of LTCC, which depends on both Ca2+ permeating through the LTCC itself and on SR Ca2+ release through the RyR. This latter effect has been suggested to rely on local rather than global Ca2+ signaling, which might parallel the nanodomain control of CDI carried out through calmodulin (CaM). Analyzing the CICR in catecholaminergic polymorphic ventricular tachycardia (CPVT) mice as a model of RyR-generated Ca2+ leak, we evidence here that increased occurrence of the discrete local SR Ca2+ releases through the RyRs (Ca2+ sparks) causea depolarizing shift in activation and a hyperpolarizing shift inisochronic inactivation of cardiac LTCC current resulting in the reduction of window current. Both increasing fast [Ca2+]i buffer capacity or depleting SR Ca2+ store blunted these changes, which could be reproduced in WT cells by RyRCa2+ leak induced with Ryanodol and CaM inhibition.Our results unveiled a new paradigm for CaM-dependent effect on LTCC gating and further the nanodomain Ca2+ control of LTCC, emphasizing the importance of spatio-temporal relationships between Ca2+ signals and CaM function

Urocortin-2 Prevents Dysregulation of Ca2+ Homeostasis and Improves Early Cardiac Remodeling After Ischemia and Reperfusion

Aims: Urocortin-2 (Ucn-2) is a potent cardioprotector against Ischemia and Reperfusion (I/R) injuries. However, little is known about its role in the regulation of intracellular Ca2+ concentration ([Ca2+]i) under I/R. Here, we examined whether the addition of Ucn-2 in reperfusion promotes cardioprotection focusing on ([Ca2+]i handling.Methods and Results: Cardiac Wistar rat model of I/R was induced by transient ligation of the left coronary artery and experiments were conducted 1 week after surgery in tissue and adult cardiomyocytes isolated from risk and remote zones. We observed that I/R promoted significant alteration in cardiac contractility as well as an increase in hypertrophy and fibrosis in both zones. The study of confocal [Ca2+]i imaging in adult cardiomyocytes revealed that I/R decreased the amplitude of [Ca2+]i transient and cardiomyocytes contraction in risk and remote zones. Interestingly, intravenous infusion of Ucn-2 before heart’s reperfusion recovered significantly cardiac contractility and prevented fibrosis, but it didn’t affect cardiac hypertrophy. Moreover, Ucn-2 recovered the amplitude of [Ca2+]i transient and modulated the expression of several proteins related to [Ca2+]i homeostasis, such as TRPC5 and Orai1 channels. Using Neonatal Rat Ventricular Myocytes (NRVM) we demonstrated that Ucn-2 blunted I/R-induced Store Operated Ca2+ Entry (SOCE), decreased the expression of TRPC5 and Orai1 as well as their interaction in reperfusion.Conclusion: Our study provides the first evidences demonstrating that Ucn-2 addition at the onset of reperfusion attenuates I/R-induced adverse cardiac remodeling, involving the [Ca2+]i handling and inhibiting the expression and interaction between TRPC5 and Orai1

Commentary on structures of the junctophilin/voltage-gated calcium channel interface reveal hot spot for cardiomyopathy mutations

International audienc

Is the Debate on the Flecainide Action on the RYR2 in CPVT Closed?

International audienc