Evidence That the Nucleotide Exchange and Hydrolysis Cycle of G Proteins Causes Acute Desensitization of G-Protein Gated Inward Rectifier K+ Channels
Abstract
The G-protein gated inward rectifier K+ channel (GIRK) is activated in vivo by the Gβγ 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.
- Publication:
-
Proceedings of the National Academy of Science
- Pub Date:
- September 1998
- DOI:
- 10.1073/pnas.95.20.11727
- Bibcode:
- 1998PNAS...9511727C