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Titolo:
Regulators of G protein signaling attenuate the G protein-mediated inhibition of N-type Ca channels
Autore:
Melliti, K; Meza, U; Fisher, R; Adams, B;
Indirizzi:
Univ Iowa, Coll Med, Dept Physiol & Biophys, Iowa City, IA 52242 USA Univ Iowa Iowa City IA USA 52242 ysiol & Biophys, Iowa City, IA 52242 USA Univ Iowa, Coll Med, Dept Pharmacol, Iowa City, IA 52242 USA Univ Iowa Iowa City IA USA 52242 Dept Pharmacol, Iowa City, IA 52242 USA
Titolo Testata:
JOURNAL OF GENERAL PHYSIOLOGY
fascicolo: 1, volume: 113, anno: 1999,
pagine: 97 - 109
SICI:
0022-1295(199901)113:1<97:ROGPSA>2.0.ZU;2-L
Fonte:
ISI
Lingua:
ENG
Soggetto:
GTPASE-ACTIVATING PROTEIN; RAT SYMPATHETIC NEURONS; BETA-GAMMA-SUBUNITS; MUSCARINIC ACETYLCHOLINE-RECEPTORS; VOLTAGE-DEPENDENT MODULATION; CALCIUM-CHANNEL; RGS PROTEINS; PHOSPHOLIPASE C-BETA-1; COUPLED RECEPTORS; POTASSIUM CHANNEL;
Keywords:
muscarinic receptors; voltage-gated calcium channel; neurosecretion; presynaptic inhibition; regulator of G protein signaling proteins;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
76
Recensione:
Indirizzi per estratti:
Indirizzo: Adams, B Univy,owa, Coll Med, Dept Physiol & Biophys, 5-660 Bowen Sci Bldg, Iowa Cit Univ Iowa 5-660 Bowen Sci Bldg Iowa City IA USA 52242 g, Iowa Cit
Citazione:
K. Melliti et al., "Regulators of G protein signaling attenuate the G protein-mediated inhibition of N-type Ca channels", J GEN PHYSL, 113(1), 1999, pp. 97-109

Abstract

Regulators of G protein signaling (RGS) proteins bind to the alpha subunits of certain heterotrimeric G proteins and greatly enhance their rate of GTP hydrolysis, thereby determining the time course of interactions among G alpha, G beta gamma, and their effecters. Voltage-gated N-type Ca channels mediate neurosecretion, and these Ca channels are powerfully inhibited by G proteins. To determine whether RGS proteins could influence Ca channel function, we recorded the activity of N-type Ca channels coexpressed in human embryonic kidney (HEK293) cells with G protein-coupled muscarinic (m2) receptors and various RGS proteins. Coexpression of full-length RGS3T, RGS3, or RGS8 significantly attenuated the magnitude of receptor-mediated Ca channelinhibition. In control cells expressing alpha 1B, alpha 2, and beta 3 Ca channel subunits and m2 receptors, carbachol (1 mu M) inhibited whole-cell currents by similar to 80% compared with only similar to 55% inhibition in cells also expressing exogenous RGS protein. A similar effect was produced by expression of the conserved core domain of RGS8. The attenuation of Ca current inhibition resulted primarily from a shift in the steady state dose-response relationship to higher agonist concentrations, with the EC50 for carbachol inhibition being similar to 18 nM in control cells vs. similar to 150 nM in RGS-expressing cells. The kinetics of Ca channel inhibition were also modified by RGS. Thus, in cells expressing RGS3T, the decay of prepulsefacilitation was slower, and recovery of Ca channels from inhibition afteragonist removal was faster than in control cells. The effects of RGS proteins on Ca channel modulation can be explained by their ability to act as GTPase-accelerating proteins for some G alpha subunits. These results suggestthat RGS proteins may play important roles in shaping the magnitude and kinetics of physiological events, such as neurosecretion, that involve G protein-modulated Ca channels.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 25/01/21 alle ore 18:21:38