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Titolo:
Residues beyond the selectivity filter of the K+ channel Kir2.1 regulate permeation and block by external Rb+ and Cs+
Autore:
Thompson, GA; Leyland, ML; Ashmole, I; Sutcliffe, MJ; Stanfield, PR;
Indirizzi:
Univ Leicester, Dept Cell Physiol & Pharmacol, Ion Channel Grp, Leicester LE1 9HN, Leics, England Univ Leicester Leicester Leics England LE1 9HN er LE1 9HN, Leics, England Univ Leicester, Dept Chem, Leicester LE1 9HN, Leics, England Univ Leicester Leicester Leics England LE1 9HN er LE1 9HN, Leics, England
Titolo Testata:
JOURNAL OF PHYSIOLOGY-LONDON
fascicolo: 2, volume: 526, anno: 2000,
pagine: 231 - 240
SICI:
0022-3751(20000715)526:2<231:RBTSFO>2.0.ZU;2-B
Fonte:
ISI
Lingua:
ENG
Soggetto:
FROG SKELETAL-MUSCLE; RECTIFIER POTASSIUM CHANNELS; SINGLE ASPARTATE RESIDUE; VOLTAGE-DEPENDENT BLOCK; INWARD RECTIFIER; ANOMALOUS RECTIFICATION; PORE; IRK1; FIBERS; MUTAGENESIS;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
37
Recensione:
Indirizzi per estratti:
Indirizzo: Stanfield, PR Univ Leicester, Dept Cell Physiol & Pharmacol, Ion Channel Grp, POB 138, Leicester LE1 9HN, Leics, England Univ Leicester POB 138 Leicester Leics England LE1 9HN gland
Citazione:
G.A. Thompson et al., "Residues beyond the selectivity filter of the K+ channel Kir2.1 regulate permeation and block by external Rb+ and Cs+", J PHYSL LON, 526(2), 2000, pp. 231-240

Abstract

1. Kir2.1 channels are blocked by Rb+ and Cs+ in a voltage-dependent manner, characteristic: of many inward rectifier K+ channels. Mutation of Ser165in the transmembrane domain M2 to Leu (S165L) abolished Rb+ blockage and lowered Cs+ blocking affinity. At negative voltages Rb+ carried large inwardcurrents.2. A model of the Kir2.1 channel, built by homology with the structure of the Streptomyces lividans K+ channel KcsA, suggested the existence of an intersubunit hydrogen bond between Ser165 and Thr141 in the channel pore-forming P-region that helps stabilise the structure of this region. However, mutations of Thr141 and Xer165 did not produce effects consistent with a hydrogen bond between these residues being essential for blockage.3. An alternative alignment between the M2 regions of Kir2.1 and KcsA suggested that Xer165 is itself a pore-lining residue, more directly affecting blockage. We were able to replace Ser165 with a variety of polar and non-polar residues, consistent with this residue being pore lining. Some of thesechanges affected channel blockage.4. We tested the hypothesis that Asp172 - a residue implicated in channel gating by polyamines - formed an additional selectivity filter by using thetriple mutant T141A/X165L/D172N. Large Rb+ and Cs+ currents were measured in this mutant.5. We propose that both Thr141 and Xer165 are likely to provide binding sites for monovalent blocking cations in wild-type channels. These residues lie beyond the carbonyl oxygen tunnel thought to form the channel selectivity filter, which the blocking cations must therefore traverse.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 01/12/20 alle ore 07:59:51