Premium
G protein modulation of recombinant P/Q‐type calcium channels by regulators of G protein signalling proteins
Author(s) -
Mark Melanie D.,
Wittemann Silke,
Herlitze Stefan
Publication year - 2000
Publication title -
the journal of physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.802
H-Index - 240
eISSN - 1469-7793
pISSN - 0022-3751
DOI - 10.1111/j.1469-7793.2000.00065.x
Subject(s) - rgs2 , g protein , gtpase activating protein , microbiology and biotechnology , regulator of g protein signaling , g protein coupled inwardly rectifying potassium channel , gq alpha subunit , voltage dependent calcium channel , g alpha subunit , heterotrimeric g protein , n type calcium channel , biology , protein subunit , gtp binding protein regulators , chemistry , hek 293 cells , gtpase , g beta gamma complex , receptor , signal transduction , biochemistry , t type calcium channel , calcium , organic chemistry , gene
1 Fast synaptic transmission is triggered by the activation of presynaptic Ca 2+ channels which can be inhibited by Gβγ subunits via G protein‐coupled receptors (GPCR). Regulators of G protein signalling (RGS) proteins are GTPase‐accelerating proteins (GAPs), which are responsible for >100‐fold increases in the GTPase activity of G proteins and might be involved in the regulation of presynaptic Ca 2+ channels. In this study we investigated the effects of RGS2 on G protein modulation of recombinant P/Q‐type channels expressed in a human embryonic kidney (HEK293) cell line using whole‐cell recordings. 2 RGS2 markedly accelerates transmitter‐mediated inhibition and recovery from inhibition of Ba 2+ currents ( I Ba ) through P/Q‐type channels heterologously expressed with the muscarinic acetylcholine receptor M2 (mAChR M2). 3 Both RGS2 and RGS4 modulate the prepulse facilitation properties of P/Q‐type Ca 2+ channels. G protein reinhibition is accelerated, while release from inhibition is slowed. These kinetics depend on the availability of G protein α and βγ subunits which is altered by RGS proteins. 4 RGS proteins unmask the Ca 2+ channel β subunit modulation of Ca 2+ channel G protein inhibition. In the presence of RGS2, P/Q‐type channels containing the β 2a and β 3 subunits reveal significantly altered kinetics of G protein modulation and increased facilitation compared to Ca 2+ channels coexpressed with the β 1b or β 4 subunit.