Effect of the Brugada syndrome mutation A39V on calmodulin regulation of Cav1.2 channels.

ABSTRACT:

Background

The L-type calcium channel Cav1.2 is important for brain and heart function. The ubiquitous calcium sensing protein calmodulin (CaM) regulates calcium dependent gating of Cav1.2 channels by reducing calcium influx, a process known as calcium-dependent inactivation (CDI). Dissecting the calcium-dependence of CaM in this process has benefited greatly from the use of mutant CaM molecules which are unable to bind calcium to their low affinity (N-lobe) and high affinity (C-lobe) binding sites. Unlike CDI, it is unknown whether CaM can modulate the activation gating of Cav1.2 channels.

Results

We examined a Cav1.2 point mutant in the N-terminus region of the channel (A39V) that has been previously linked to Brugada syndrome. Using mutant CaM constructs in which the N- a

SUBMITTER: Simms BA 

PROVIDER: S-EPMC4012176 | biostudies-literature | 2014 Apr

REPOSITORIES: biostudies-literature