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Asymmetrical Contributions of Subunit Pore Regions to Ion Selectivity in an Inward Rectifier K⁺ Channel

Silverman, Scott K. and Lester, Henry A. and Dougherty, Dennis A. (1998) Asymmetrical Contributions of Subunit Pore Regions to Ion Selectivity in an Inward Rectifier K⁺ Channel. Biophysical Journal, 75 (3). pp. 1330-1339. ISSN 0006-3495. PMCID PMC1299807. doi:10.1016/s0006-3495(98)74051-2.

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We have investigated aspects of ion selectivity in K⁺ channels by functional expression of wild-type and mutant heteromultimeric G protein-coupled inward-rectifier K⁺ (GIRK) channels in Xenopus oocytes. Within the K⁺ channel pore (P) region signature sequence, a large number of point mutations in GIRK1 and GIRK4 subunits have been made at a key tyrosine residue—the “signature” tyrosine of the GYG. Studies of mutant GIRK1/GIRK4 heteromultimers reveal that the GIRK1 and GIRK4 subunits contribute asymmetrically to K⁺ selectivity. The signature tyrosine of GIRK1 can be mutated to many different residues while retaining selectivity; in contrast, the analogous position in GIRK4 must be tyrosine for maximum selectivity. Other residues of the P region also contribute to selectivity, and studies with GIRK1/GIRK4 chimeras reveal that an intact, heteromultimeric P region is necessary and sufficient for optimal K⁺ selectivity. We propose that the GIRK1 and GIRK4 P regions play roles similar to the two P regions of an emerging family of K⁺ channels whose subunits each have two P regions connected in tandem. We find different consequences between similar mutations in inward-rectifier and voltage-gated K⁺ channels, which suggests that the pore structures and selectivity mechanisms in the two classes of channel may not be identical. We confirm that GIRK4 subunits alone can form functional channels in oocytes, but we find that these channels are measurably permeable to Na⁺ and Ca²⁺.

Item Type:Article
Related URLs:
URLURL TypeDescription CentralArticle
Silverman, Scott K.0000-0001-8166-3460
Lester, Henry A.0000-0002-5470-5255
Dougherty, Dennis A.0000-0003-1464-2461
Additional Information:© 1998 The Biophysical Society. Published by Elsevier Inc. Received 18 February 1998, Accepted 2 June 1998. We thank Drs. Paulo Kofuji and Craig Doupnik for discussions. This work was supported by grants from the National Institutes of Health (NS34407 and GM29836).
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Issue or Number:3
PubMed Central ID:PMC1299807
Record Number:CaltechAUTHORS:20200513-104033054
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Official Citation:Silverman SK, Lester HA, Dougherty DA. Asymmetrical contributions of subunit pore regions to ion selectivity in an inward rectifier K+ channel. Biophys J. 1998;75(3):1330‐1339. doi:10.1016/S0006-3495(98)74051-2
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:103176
Deposited By: Rebecca Minjarez
Deposited On:18 May 2020 21:43
Last Modified:16 Nov 2021 18:19

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