Arrhythmogenic calmodulin mutations impede activation of small-conductance calcium-activated potassium current.

ABSTRACT:

Background

Apamin-sensitive small-conductance calcium-activated potassium (SK) channels are gated by intracellular Ca(2+) through a constitutive interaction with calmodulin.

Objective

We hypothesize that arrhythmogenic human calmodulin mutations impede activation of SK channels.

Methods

We studied 5 previously published calmodulin mutations (N54I, N98S, D96V, D130G, and F90L). Plasmids encoding either wild-type or mutant calmodulin were transiently transfected into human embryonic kidney 293 cells that stably express subtype 2 of SK protein channels (SK2 cells). Whole-cell voltage-clamp recording was used to determine apamin-sensitive current densities. We also performed optical mapping studies in normal murine hearts to determine the effects of apamin in hearts with

SUBMITTER: Yu CC 

PROVIDER: S-EPMC4958519 | biostudies-literature | 2016 Aug

REPOSITORIES: biostudies-literature