RGS proteins reconstitute the rapid gating kinetics of Gβγ-activated inwardly rectifying K+ channels
Open Access
- 16 September 1997
- journal article
- research article
- Published by Proceedings of the National Academy of Sciences in Proceedings of the National Academy of Sciences of the United States of America
- Vol. 94 (19), 10461-10466
- https://doi.org/10.1073/pnas.94.19.10461
Abstract
G protein-gated inward rectifier K+ (GIRK) channels mediate hyperpolarizing postsynaptic potentials in the nervous system and in the heart during activation of Gα(i/o)-coupled receptors. In neurons and cardiac atrial cells the time course for receptor-mediated GIRK current deactivation is 20–40 times faster than that observed in heterologous systems expressing cloned receptors and GIRK channels, suggesting that an additional component(s) is required to confer the rapid kinetic properties of the native transduction pathway. We report here that heterologous expression of “regulators of G protein signaling” (RGS proteins), along with cloned G protein-coupled receptors and GIRK channels, reconstitutes the temporal properties of the native receptor → GIRK signal transduction pathway. GIRK current waveforms evoked by agonist activation of muscarinic m2 receptors or serotonin 1A receptors were dramatically accelerated by coexpression of either RGS1, RGS3, or RGS4, but not RGS2. For the brain-expressed RGS4 isoform, neither the current amplitude nor the steady-state agonist dose-response relationship was significantly affected by RGS expression, although the agonist-independent “basal” GIRK current was suppressed by ≈40%. Because GIRK activation and deactivation kinetics are the limiting rates for the onset and termination of “slow” postsynaptic inhibitory currents in neurons and atrial cells, RGS proteins may play crucial roles in the timing of information transfer within the brain and to peripheral tissues.Keywords
This publication has 39 references indexed in Scilit:
- Time Resolved Kinetics of Direct Gβ1γ2 Interactions with the Carboxyl Terminus of Kir3.4 Inward Rectifier K+ Channel SubunitsNeuropharmacology, 1996
- RGS10 is a selective activator of Gαi GTPase activityNature, 1996
- RGS family members: GTPase-activating proteins for heterotrimeric G-protein α-subunitsNature, 1996
- Inhibition of an inwardly rectifying K+ channel by G-protein α-subunitsNature, 1996
- Regulation of Phospholipase C-β1 by Gq and m1 Muscarinic Cholinergic ReceptorPublished by Elsevier BV ,1996
- Inhibition of G-protein-mediated MAP kinase activation by a new mammalian gene familyNature, 1996
- Gβγ Binds Directly to the G Protein-gated K+ Channel, IKAChPublished by Elsevier BV ,1995
- Identification of structural elements involved in G protein gating of the GIRK1 potassium channelNeuron, 1995
- A G protein-gated K channel is activated via beta 2-adrenergic receptors and G beta gamma subunits in Xenopus oocytes.The Journal of general physiology, 1995
- G PROTEINS: TRANSDUCERS OF RECEPTOR-GENERATED SIGNALSAnnual Review of Biochemistry, 1987