RGS proteins reconstitute the rapid gating kinetics of Gβγ-activated inwardly rectifying K+ channels

Craig A. Doupnik, Norman Davidson, Henry A. Lester, Paulo Kofuji

Research output: Contribution to journalArticle

287 Citations (Scopus)

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 co-expression 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.

Original languageEnglish (US)
Pages (from-to)10461-10466
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume94
Issue number19
DOIs
StatePublished - Sep 16 1997

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GTP-Binding Protein Regulators
Inwardly Rectifying Potassium Channel
Muscarinic M2 Receptors
Neurons
Inhibitory Postsynaptic Potentials
Synaptic Potentials
Receptor, Serotonin, 5-HT1A
Brain
G-Protein-Coupled Receptors
GTP-Binding Proteins
Nervous System
Signal Transduction
Protein Isoforms

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RGS proteins reconstitute the rapid gating kinetics of Gβγ-activated inwardly rectifying K+ channels. / Doupnik, Craig A.; Davidson, Norman; Lester, Henry A.; Kofuji, Paulo.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 94, No. 19, 16.09.1997, p. 10461-10466.

Research output: Contribution to journalArticle

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