Role of the S4 segment in a voltage-dependent calcium-sensitive potassium (hSlo) channel

被引:100
作者
Díaz, L
Meera, P
Amigo, J
Stefani, E
Alvarez, O
Toro, L
Latorre, R
机构
[1] Ctr Estudios Cient, Valdivia 9, Chile
[2] Univ Chile, Fac Ciencias, Dept Biol, Santiago, Chile
[3] Univ Calif Los Angeles, Brain Res Inst, Los Angeles, CA 90095 USA
[4] Univ Calif Los Angeles, Dept Anesthesiol, Los Angeles, CA 90095 USA
[5] Univ Calif Los Angeles, Dept Physiol, Los Angeles, CA 90095 USA
[6] Univ Calif Los Angeles, Dept Mol & Med Pharmacol, Los Angeles, CA 90095 USA
关键词
D O I
10.1074/jbc.273.49.32430
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
We investigated the role of individual charged residues of the S4 region of a MaxiK channel (hSlo) in channel gating, We measured macroscopic currents induced by wild type (WT) and point mutants of hSlo in inside-out membrane patches of Xenopus laevis oocytes, Of all the residues tested, only neutralizations of Arg-210 and Arg-213 were associated with a reduction in the number of gating charges as determined using the limiting slope method. Channel activation in WT and mutant channels was interpreted using an allosteric model. Mutations R207Q, R207E, and R210N facilitated channel opening in the absence of Ca2+; however, this facilitation was not observed in the channels Ca2+-bound state. Mutation R2136 behaved similarly to the WT channel in the absence of Ca2+, but Ca2+ was unable to stabilize the open state to the same extent as it does in the WT. Mutations R207Q, R207E, R210N, and R213Q reduced the coupling between Ca2+ binding and channel opening when compared with the WT. Mutations L204R, L204H, Q216R, E219Q, and E219K in the 54 domain showed a similar phenotype to the WT channel. We conclude that the S4 region in the hSlo channel is part of the voltage sensor and that only two charged amino acid residues in this region (Arg-210 and Arg-213) contribute to the gating valence of the channel.
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收藏
页码:32430 / 32436
页数:7
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