Arrhythmogenic calmodulin variants D131E and Q135P disrupt interaction with the L-type voltage-gated Ca²⁺ channel (Ca_v1.2) and reduce Ca²⁺-dependent inactivation.

ABSTRACT:

Aim

Long QT syndrome (LQTS) and catecholaminergic polymorphism ventricular tachycardia (CPVT) are inherited cardiac disorders often caused by mutations in ion channels. These arrhythmia syndromes have recently been associated with calmodulin (CaM) variants. Here, we investigate the impact of the arrhythmogenic variants D131E and Q135P on CaM's structure-function relationship. Our study focuses on the L-type calcium channel Ca_v1.2, a crucial component of the ventricular action potential and excitation-contraction coupling.

Methods

We used circular dichroism (CD), ¹H-¹⁵N HSQC NMR, and trypsin digestion to determine the structural and stability properties of CaM variants. The affinity of CaM for Ca²⁺ and interaction of Ca²⁺

SUBMITTER: Gupta N 

PROVIDER: S-EPMC11742489 | biostudies-literature | 2025 Feb

REPOSITORIES: biostudies-literature