Intrinsic gating properties of a cloned G Protein-activated inward rectifier K+ channel

Craig A. Doupnik, Nancy F. Lim, Paulo Kofuji, Norman Davidson, Henry A. Lester

Research output: Contribution to journalArticlepeer-review

28 Scopus citations

Abstract

The voltage-, time-, and K+ properties of a G proteinactivated inwardly rectifying K+ channel (GIRK1/KGA/Kir3.1) cloned from rat atrium were studied in Xenopus oocytes under two-electrode voltage clamp. During maintained G protein activation and in the presence of high external K+ (Vk = 0 mV), voltage jumps from Vk to negative membrane potentials activated inward GIRK1 K+ currents with three distinct time-resolved current components. GIRK1 current activation consisted of an instantaneous component that was followed by two components with time constants τ~50 ms and τ~0400 ms. These activation time constants were weakly voltage dependent, increasing approximately twofold with maximal hyperpolarization from Vk. Voltage-dependent GIRK1 availability, reveaied by tail currents at -80 mV after long prepulses, was greatest at potentials negative to Vk and declined to a plateau of approximately half the maximal level at positive voltages. Voltage-dependent GIRK1 availability shifted with VK and was half maximal at VK-20 mV; the equivalent gating charge was ~6 e. The voltage-dependent gating parameters of GIRK1 did not significantly differ for G protein activation by three heterologously expressed signaling pathways: m2 muscarinic receptors, serotonin 1A receptors, or G protein βα2 subunits. Voltage dependence was also unaffected by agonist concentration. These results indicate that the voltage-dependent gating properties of GIRK1 are not due to extrinsic factors such as agonist-receptor interactions and G proteinchannel coupling, but instead are analogous to the intrinsic gating behaviors of other inwardly rectifying K+ channels.

Original languageEnglish (US)
Pages (from-to)1-23
Number of pages23
JournalJournal of General Physiology
Volume106
Issue number1
DOIs
StatePublished - Jul 1 1995

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