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Intrinsic Gating Properties of a Cloned G Protein-activated Inward Rectifier K^+ Channel

Doupnik, Craig A. and Lim, Nancy F. and Kofuji, Paulo and Davidson, Norman and Lester, Henry A. (1995) Intrinsic Gating Properties of a Cloned G Protein-activated Inward Rectifier K^+ Channel. Journal of General Physiology, 106 (1). pp. 1-23. ISSN 0022-1295. PMCID PMC2229253. doi:10.1085/jgp.106.1.1.

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The voltage-, time-, and K^+-dependent properties of a G protein-activated 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^+ (V_K = 0 mV), voltage jumps from V_K 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 T_f~50 ms and T_s~400 ms. These activation time constants were weakly voltage dependent, increasing approximately twofold with maximal hyperpolarization from V_K. Voltage-dependent GIRK1 availability, revealed by tail currents at -80 mV after long prepulses, was greatest at potentials negative to V_K and declined to a plateau of approximately half the maximal level at positive voltages. Voltage-dependent GIRK1 availability shifted with V_K and was half maximal at V_K -20 mV; the equivalent gating charge was ~1.6 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 β1y2 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 protein-channel coupling, but instead are analogous to the intrinsic gating behaviors of other inwardly rectifying K^+ channels.

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Lester, Henry A.0000-0002-5470-5255
Additional Information:© 1995 Rockefeller University Press. Original version received 2 December 1994 and accepted version received 29 March 1995. Published July 1, 1995. We thank Heather Davis and Brad Henkle for preparation of oocytes. This work was supported by fellowships from the American Heart Association (C. A. Doupnik) and the National Institutes of Health (NIH) (N. F. Lim) and by NIH grants GM29836 and MH49176.
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American Heart AssociationUNSPECIFIED
Issue or Number:1
PubMed Central ID:PMC2229253
Record Number:CaltechAUTHORS:20120216-103326772
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Official Citation:Intrinsic gating properties of a cloned G protein-activated inward rectifier K+ channel. C A Doupnik, N F Lim, P Kofuji, N Davidson, and H A Lester J Gen Physiol 1995 106:1-23. Published July 1, 1995, doi:10.1085/jgp.106.1.1
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:29337
Deposited By: Ruth Sustaita
Deposited On:16 Feb 2012 19:02
Last Modified:09 Nov 2021 17:06

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