Current view on regulation of voltage-gated sodium channels by calcium and auxiliary proteins.
Journal Article (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
- PMC5338247
Electronic International Standard Serial Number (EISSN)
- 1469-896X
Digital Object Identifier (DOI)
- 10.1002/pro.2960
Language
- eng
Conference Location
- United States