Inhibition of Voltage-Gated Calcium Channels by RGK Proteins

Title:Inhibition of Voltage-Gated Calcium Channels by RGK Proteins

Volume: 8

Author(s): Zafir Buraei and Jian Yang

Affiliation:

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

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 (Ca_vβ) 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 Ca_vβ is required for all forms of RGK inhibition, not all inhibition is mediated by the RGK-Ca_vβ interaction. Some RGK proteins also interact directly with the pore-forming α₁ subunit of some types of VGCCs (Ca_vα₁). 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.

Cite this article as:

Buraei Zafir and Yang Jian, Inhibition of Voltage-Gated Calcium Channels by RGK Proteins, Current Molecular Pharmacology 2015; 8 (2) . https://dx.doi.org/10.2174/1874467208666150507105613