Mutations throughout the S6 region of the hKv1.5 channel alter the stability of the activation gate.
Mutations throughout the S6 region of the hKv1.5 channel alter the stability of the activation gate.
复制标题
hKv1.5 通道 S6 区域的突变改变了激活门的稳定性。
DOI：
10.1152/ajpcell.00232.2001
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发表时间：
2002
期刊：
影响因子：
--
通讯作者：
Snyders,DirkJ
中科院分区：
文献类型：
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作者：
Rich,ThomasC;Yeola,SaritaW;Tamkun,MichaelM;Snyders,DirkJ
首次发表于2001年9月21日; 10.1152/ ajpcell.00232.2001。电压门控K+通道的S6段被认为有助于打开中央渗透途径的门。在这里，我们提出的证据表明，整个细胞质端的S6突变强烈影响hKv1.5通道门控特性。在位置T505、V512和S515处的hKv1.5的修饰导致激活的电压依赖性的大的负位移，而在位置Y519处的修饰导致负（Y519 N）和正（Y519 F）位移。当针对改变的电压敏感性进行调整时，突变通道的激活动力学与野生型（WT）通道的激活动力学相似;然而，突变T505 I、T505 V、V512 A和V512 M的失活动力学[时间常数（τ）分别= 35、250、170和420 ms]仍慢于WT（τ = 8.3 ms）。此外，WT通道的失活是高度温度敏感的。然而，T505 I和V512 A通道的失活在很大程度上是温度不敏感的。总之，这些数据表明，S6中的突变通过改变开放状态稳定性将激活与失活解耦，并且高度保守的Pro-X-Pro序列两侧的残基影响通道门控期间S6的运动。
First published September 21, 2001; 10.1152/ ajpcell.00232.2001.—The S6 segment of voltage-gated K+channels is thought to contribute to the gate that opens the central permeation pathway. Here we present evidence that mutations throughout the cytoplasmic end of S6 strongly influence hKv1.5 channel gating characteristics. Modification of hKv1.5 at positions T505, V512, and S515 resulted in large negative shifts in the voltage dependence of activation, whereas modifications at position Y519 resulted in negative (Y519N) and positive (Y519F) shifts. When adjusted for the altered voltage sensitivity, activation kinetics of mutated channels were similar to those of the wild-type (WT) channel; however, deactivation kinetics of mutations T505I, T505V, V512A, and V512M [time constant (τ) = 35, 250, 170, and 420 ms, respectively] were still slower than WT (τ = 8.3 ms). In addition, deactivation of WT channels was highly temperature sensitive. However, deactivation of T505I and V512A channels was largely temperature insensitive. Together, these data suggest that mutations in S6 decouple activation from deactivation by altering the open-state stability and that residues on both sides of the highly conserved Pro-X-Pro sequence influence the movement of S6 during channel gating.