Impaired calcium-calmodulin-dependent inactivation of Cav1.2 contributes to loss of sarcoplasmic reticulum calcium release refractoriness in mice lacking calsequestrin 2

Our findings reveal that the intra-SR protein Casq2 is largely responsible for the phenomenon of SR Ca2 + release refractoriness in murine ventricular myocytes. We also report a novel mechanism of impaired Ca2 +-CaM-dependent inactivation of Cav1.2, which contributes to the loss of SR Ca2 + release refractoriness in the Casq2 KO mouse model and, therefore, may further increase risk for ventricular arrhythmia in vivo.