Inhibition of Voltage-Gated Calcium Channels by RGK Proteins

Author(s): Zafir Buraei, Jian Yang

Journal Name: Current Molecular Pharmacology

Volume 8 , Issue 2 , 2015

Become EABM
Become Reviewer
Call for Editor

Graphical Abstract:


Due to their essential biological roles, voltage-gated calcium channels (VGCCs) are regulated by a myriad of molecules and mechanisms. Fifteen years ago, RGK proteins were discovered to bind the VGCC β subunit (Cavβ) and potently inhibit high-voltage activated Ca2+ channels. RGKs (Rad, Rem, Rem2 and Gem/Kir) are a family of monomeric small GTPases belonging to the superfamily of Ras GTPases. They exert dual inhibitory effects on VGCCs, decreasing surface expression and suppressing surface channels through immobilization of the voltage sensor or reduction of channel open probability. While Cavβ is required for all forms of RGK inhibition, not all inhibition is mediated by the RGK-Cavβ interaction. Some RGK proteins also interact directly with the pore-forming α1 subunit of some types of VGCCs (Cavα1). Importantly, RGK proteins tonically inhibit VGCCs in native cells, regulating cardiac and neural functions. This minireview summarizes the mechanisms, molecular determinants, and physiological impact of RGK inhibition of VGCCs.

Keywords: Action potential, calcium, cardiac, heart, GTP-ase, Ion channels, neurotransmitter release, regulation.

Rights & PermissionsPrintExport Cite as

Article Details

Year: 2015
Page: [180 - 187]
Pages: 8
DOI: 10.2174/1874467208666150507105613
Price: $65

Article Metrics

PDF: 31
PRC: 2