Suppression of ryanodine receptor function prolongs Ca2+ release refractoriness and promotes cardiac alternans in intact hearts.

ABSTRACT: Beat-to-beat alternations in the amplitude of the cytosolic Ca²⁺ transient (Ca²⁺ alternans) are thought to be the primary cause of cardiac alternans that can lead to cardiac arrhythmias and sudden death. Despite its important role in arrhythmogenesis, the mechanism underlying Ca²⁺ alternans remains poorly understood. Here, we investigated the role of cardiac ryanodine receptor (RyR2), the major Ca²⁺ release channel responsible for cytosolic Ca²⁺ transients, in cardiac alternans. Using a unique mouse model harboring a suppression-of-function (SOF) RyR2 mutation (E4872Q), we assessed the effect of genetically suppressing RyR2 function on Ca²⁺ and action potential duration (APD) alternans in intact hearts, and electrocardiogram

SUBMITTER: Zhong X 

PROVIDER: S-EPMC5522810 | biostudies-literature | 2016 Nov

REPOSITORIES: biostudies-literature