Evidence that the nucleotide exchange and hydrolysis cycle of G proteins causes acute desensitization of G-protein gated inward rectifier K+ channels.
作者:
Chuang(H H),Yu(M),Jan(Y N),Jan(L Y)
状态:
发布时间1998-10-22
, 更新时间 2016-10-19
期刊:
Proc Natl Acad Sci U S A
摘要:
The G-protein gated inward rectifier K+ channel (GIRK) is activated in vivo by the Gbeta gamma subunits liberated upon Gi-coupled receptor activation. We have recapitulated the acute desensitization of receptor-activated GIRK currents in heterologous systems and shown that it is a membrane-delimited process. Its kinetics depends on the guanine nucleotide species available and could be accounted for by the nucleotide exchange and hydrolysis cycle of G proteins. Indeed, acute desensitization is abolished by nonhydrolyzable GTP analogues. Whereas regulators of G-protein signaling (RGS) proteins by their GTPase-activating protein activities are regarded as negative regulators, a positive regulatory function of RGS4 is uncovered in our study; the opposing effects allow RGS4 to potentiate acute desensitization without compromising GIRK activation.