Current view on regulation of voltage-gated sodium channels by calcium and auxiliary proteins.

Published

Journal Article (Review)

In cardiac and skeletal myocytes, and in most neurons, the opening of voltage-gated Na(+) channels (NaV channels) triggers action potentials, a process that is regulated via the interactions of the channels' intercellular C-termini with auxiliary proteins and/or Ca(2+) . The molecular and structural details for how Ca(2+) and/or auxiliary proteins modulate NaV channel function, however, have eluded a concise mechanistic explanation and details have been shrouded for the last decade behind controversy about whether Ca(2+) acts directly upon the NaV channel or through interacting proteins, such as the Ca(2+) binding protein calmodulin (CaM). Here, we review recent advances in defining the structure of NaV intracellular C-termini and associated proteins such as CaM or fibroblast growth factor homologous factors (FHFs) to reveal new insights into how Ca(2+) affects NaV function, and how altered Ca(2+) -dependent or FHF-mediated regulation of NaV channels is perturbed in various disease states through mutations that disrupt CaM or FHF interaction.

Full Text

Duke Authors

Cited Authors

  • Pitt, GS; Lee, S-Y

Published Date

  • September 2016

Published In

Volume / Issue

  • 25 / 9

Start / End Page

  • 1573 - 1584

PubMed ID

  • 27262167

Pubmed Central ID

  • 27262167

Electronic International Standard Serial Number (EISSN)

  • 1469-896X

Digital Object Identifier (DOI)

  • 10.1002/pro.2960

Language

  • eng

Conference Location

  • United States