Redox modification of ryanodine receptors underlies calcium alternans in a canine model of sudden cardiac death

Abstract

Redox modulation of RyRs promotes generation of Ca(2+) alternans by enhancing the steepness of the Ca(2+) release-load relationship and thereby providing a substrate for post-MI arrhythmias.

NADPH Oxidase-Dependent Regulation of T-Type Ca2+Channels and Ryanodine Receptors Mediate the Augmented Exocytosis of Catecholamines from Intermittent Hypoxia-Treated Neonatal Rat Chromaffin Cells

“…Blockade of RyRs restored basal [Ca 2ϩ ] i levels in IH cells to levels seen in control cells, implying that constitutive activation of RyRs mediates the elevated basal [Ca 2ϩ ] i levels in IH cells. We further demonstrate that IH leads to NOX/ROSdependent S-glutathionylation of RyR2, which is known to constitutively activate RyRs (Murayama et al, 1999;Zissimopoulos and Lai, 2006;Bull et al, 2008;Huddleston et al, 2008;Belevych et al, 2009). These observations taken together demonstrate that NOX/ROS signaling activates RyRs by transcriptional upregulation as well as by posttranslational modifications involving S-glutathionylation in IH-treated neonatal chromaffin cells resulting in constitutive activation of RyRs.…”

“…However, the source(s) of intracellular Ca 2ϩ stores and the mechanism by which IH mobilizes Ca 2ϩ stores has not been explored. Ryanodine receptors (RyRs) are one of the major regulators of mobilization of intracellular Ca 2ϩ stores (Simpson et al, 1995;Alonso et al, 1999), and ROS are potent activators of RyRs (Murayama et al, 1999;Zissimopoulos and Lai, 2006;Bull et al, 2008;Huddleston et al, 2008;Belevych et al, 2009). Therefore, in the present study, we examined the impact of neonatal IH on T-type Ca 2ϩ channels and RyRs expression in adrenal chromaffin cells and determined their roles in neurotransmitter release.…”

Protective effects of saffron (Crocus sativus) against lethal ventricular arrhythmias induced by heart reperfusion in rat: A potential anti-arrhythmic agent

“…The shift of the cellular redox potential to increase oxidation can enhance action potential heterogeneity by modulating ion channels (Brown & O'Rourke, 2010). In addition, increased oxidation directly activates SarcKATP (sarcolemmal-ATPdependent potassium) channels (Tokube et al, 1996(Tokube et al, , 1998 and changes the inactivation kinetics of L-type calcium channels (Belevych et al, 2009). SarcKATP channels opening reduces the action potential duration and effective refractory period (Aidonidis et al, 2009;Ferrier & Howlett, 2005) which in turn increases the incidence of cardiac arrhythmia (Billman, 2008;Billman et al, 2004).…”

Role of chronic ryanodine receptor phosphorylation in heart failure and β-adrenergic receptor blockade in mice

“…32). Furthermore, oxidizing agents have been shown to promote RyR2-mediated SR Ca 2+ leak, and RyR2 was reported to be oxidized in failing hearts from a canine model of HF (33,34). We also examined Cys-nitrosylation of RyR2, since Cys-nitrosylation has been reported to cause depletion of calstabin1 from the RyR1 complex in skeletal muscle (35,36) and we have recently shown that Cys-nitrosylation of RyR1 and RyR2 in skeletal and cardiac muscles from a mouse model of Duchenne muscular dystrophy causes depletion of calstabin1 and calstabin2 from RyR1 and RyR2s, respectively (36,37).…”