Title | Current view on regulation of voltage-gated sodium channels by calcium and auxiliary proteins. |
Publication Type | Journal Article |
Year of Publication | 2016 |
Authors | Pitt, GS, Lee, S-Y |
Journal | Protein Sci |
Volume | 25 |
Issue | 9 |
Pagination | 1573-84 |
Date Published | 2016 Sep |
ISSN | 1469-896X |
Abstract | 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. |
DOI | 10.1002/pro.2960 |
Alternate Journal | Protein Sci. |
PubMed ID | 27262167 |
PubMed Central ID | PMC5338247 |
Grant List | DP2 OD008380 / OD / NIH HHS / United States R01 HL122967 / HL / NHLBI NIH HHS / United States |