A Mechanism of Calmodulin Modulation of the Human Cardiac Sodium Channel.

ABSTRACT: The function of the human cardiac sodium channel (Na_V1.5) is modulated by the Ca²⁺ sensor calmodulin (CaM), but the underlying mechanism(s) are controversial and poorly defined. CaM has been reported to bind in a Ca²⁺-dependent manner to two sites in the intracellular loop that is critical for inactivation of Na_V1.5 (inactivation gate [IG]). The affinity of CaM for the complete IG was significantly stronger than that of fragments that lacked both complete binding sites. Structural analysis by nuclear magnetic resonance, crystallographic, and scattering approaches revealed that CaM simultaneously engages both IG sites using an extended configuration. Patch-clamp recordings for wild-type and mutant channels with an impaired CaM-IG interaction revea

SUBMITTER: Johnson CN 

PROVIDER: S-EPMC5932218 | biostudies-literature | 2018 May

REPOSITORIES: biostudies-literature