For information about COVID-19, including symptoms and prevention, please read our COVID-19 patient guide. Please also consider supporting Weill Cornell Medicine’s efforts against the pandemic.
Pitt Lab

You are here

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

TitleCurrent view on regulation of voltage-gated sodium channels by calcium and auxiliary proteins.
Publication TypeJournal Article
Year of Publication2016
AuthorsPitt GS, Lee S-Y
JournalProtein Sci
Date Published2016 Sep

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.

Alternate JournalProtein Sci.
PubMed ID27262167
PubMed Central IDPMC5338247
Grant ListDP2 OD008380 / OD / NIH HHS / United States
R01 HL122967 / HL / NHLBI NIH HHS / United States