Arrhythmia-associated calmodulin variants interact with KCNQ1 to confer aberrant membrane trafficking and function.

ABSTRACT: Missense variants in calmodulin (CaM) predispose patients to arrhythmias associated with high mortality rates ("calmodulinopathy"). As CaM regulates many key cardiac ion channels, an understanding of disease mechanism associated with CaM variant arrhythmias requires elucidating individual CaM variant effects on distinct channels. One key CaM regulatory target is the KCNQ1 (K_V7.1) voltage-gated potassium channel that carries the I_Ks current. Yet, relatively little is known as to how CaM variants interact with KCNQ1 or affect its function. Here, we take a multipronged approach employing a live-cell fluorescence resonance energy transfer binding assay, fluorescence trafficking assay, and functional electrophysiology to characterize >10 arrhythmia-associated CaM variants

SUBMITTER: Kang PW 

PROVIDER: S-EPMC10642763 | biostudies-literature | 2023 Nov

REPOSITORIES: biostudies-literature