Functional Calsequestrin-1 Is Expressed in the Heart and Its Deficiency Is Causally Related to Malignant Hyperthermia-Like Arrhythmia

Abstract

Casq1 is expressed in the heart, where it regulates sarcoplasmic reticulum Ca²⁺ release and heart rate. Casq1 deficiency independently causes MH/EHS-like ventricular arrhythmia by trigger-induced Casq1 oligomerization and a relief of its inhibitory effect on ryanodine receptor-2-mediated Ca²⁺ release, thus revealing a new inherited arrhythmia and a novel mechanism for MH/EHS arrhythmogenesis.