Asymmetrical contributions of subunit pore regions to ion selectivity in an inward rectifier K+ channel

Scott K. Silverman, Henry A. Lester, Dennis A. Dougherty

Research output: Contribution to journalArticle

Abstract

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+.

Original languageEnglish (US)
Pages (from-to)1330-1339
Number of pages10
JournalBiophysical journal
Volume75
Issue number3
DOIs
StatePublished - Sep 1998

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Inwardly Rectifying Potassium Channel
Tyrosine
Ions
Oocytes
Voltage-Gated Potassium Channels
Xenopus
GTP-Binding Proteins
Point Mutation
Mutation

ASJC Scopus subject areas

  • Biophysics

Cite this

Asymmetrical contributions of subunit pore regions to ion selectivity in an inward rectifier K+ channel. / Silverman, Scott K.; Lester, Henry A.; Dougherty, Dennis A.

In: Biophysical journal, Vol. 75, No. 3, 09.1998, p. 1330-1339.

Research output: Contribution to journalArticle

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