Dysregulated Zn²⁺ homeostasis impairs cardiac type-2 ryanodine receptor and mitsugumin 23 functions, leading to sarcoplasmic reticulum Ca²⁺ leakage.

ABSTRACT: Aberrant Zn²⁺ homeostasis is associated with dysregulated intracellular Ca²⁺ release, resulting in chronic heart failure. In the failing heart a small population of cardiac ryanodine receptors (RyR2) displays sub-conductance-state gating leading to Ca²⁺ leakage from sarcoplasmic reticulum (SR) stores, which impairs cardiac contractility. Previous evidence suggests contribution of RyR2-independent Ca²⁺ leakage through an uncharacterized mechanism. We sought to examine the role of Zn²⁺ in shaping intracellular Ca²⁺ release in cardiac muscle. Cardiac SR vesicles prepared from sheep or mouse ventricular tissue were incorporated into phospholipid bilayers under voltage-clamp conditions, and the direct action of Zn²⁺ on

SUBMITTER: Reilly-O'Donnell B 

PROVIDER: S-EPMC5555195 | biostudies-literature | 2017 Aug

REPOSITORIES: biostudies-literature