Molecular basis for different pore properties of potassium channels from the rat brain Kv1 gene family

被引:27
作者
GomezHernandez, JM
Lorra, C
Pardo, LA
Stuhmer, W
Pongs, O
Heinemann, SH
Elliott, AA
机构
[1] MAX PLANCK GESELL,AG MOL & ZELLULARE BIOPHYS,D-07747 JENA,GERMANY
[2] MPI EXPT MED,D-37075 GOTTINGEN,GERMANY
[3] ZMNH,INST NEURALE SIGNALVERARBEITUNG,D-20246 HAMBURG,GERMANY
[4] INST NEUROBIOL,D-69120 HEIDELBERG,GERMANY
[5] UNIV DUNDEE,DEPT ANAT & PHYSIOL,DUNDEE DD1 4HN,SCOTLAND
来源
PFLUGERS ARCHIV-EUROPEAN JOURNAL OF PHYSIOLOGY | 1997年 / 434卷 / 06期
基金
英国惠康基金;
关键词
potassium channel; single channel; Xenopus oocyte; tetraethylammonium; magnesium;
D O I
10.1007/s004240050449
中图分类号
Q4 [生理学];
学科分类号
071003 ;
摘要
Members of the rat brain Kv1 family of cloned potassium channels are structurally highly homologous, but have diverse conductance and pharmacological characteristics. Here we present data on the effects of mutating residues K533 in the P-region and H471 in the S4-S5 linker of Kv1.4 to their equivalent residues in Kv1.1 and Kv1.6 on single-channel conductance and sensitivity to external tetraethylammonium cations (TEA(+)) and internal Mg2+. Exchange of residue K533 for its equivalent residue (Y) in Kv1.1 and Kv1.6 increased the single-channel conductance at both negative and positive potentials. This mutation is known to reduce the IC50 for external TEA(+) from > 100 mM to 0.6 mM, almost identical to that for Kv1.1 (0.53 mM). We have now found that the additional exchange of residue H471 for the equivalent residue (K) in Kv1.6 increased the IC50 for external TEA(+) from 0.6 mM (Kv1.4K533Y) to 2.39 mM; this is very close to that for wild-type Kv1.6 channels (2.84 mM). The mutation H471K alone was ineffective. We thus provide evidence that the S4-S5 linker does contribute to the channel's inner-port region. Data on the block of Kv1 channels by internal Mg2+ indicate that while the binding site is probably situated within the deep-pore region, its exact location may be channel specific.
引用
收藏
页码:661 / 668
页数:8
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