MODULATION OF K+ CURRENT BY FREQUENCY AND EXTERNAL [K+] - A TALE OF 2 INACTIVATION MECHANISMS
MODULATION OF K+ CURRENT BY FREQUENCY AND EXTERNAL [K+] - A TALE OF 2 INACTIVATION MECHANISMS
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DOI：
10.1016/0896-6273(95)90185-x
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发表时间：
1995-10-01
期刊：
影响因子：
16.2
通讯作者：
YELLEN, G
中科院分区：
文献类型：
--
作者：
BAUKROWITZ, T;YELLEN, G
电压激活的 K+ 电流及其失活特性对于控制神经元和其他可兴奋细胞中的频率依赖性信号传导非常重要。已经描述了 K+ 通道失活的两种不同分子机制：N 型，涉及细胞内系留阻滞剂对开放通道的快速闭塞；C 型，涉及孔的细胞外口的较慢变化。我们发现 Shaker 通道的频率依赖性累积失活对生理范围内细胞外 [K+] 的变化非常敏感，在低 [K+](out) 时失活更多，并且是 N 型和 C 型失活相互作用的结果。 N型失活通过两种机制增强C型失活。首先，它抑制向外的 K+ 通量，该通量通常填充外部离子位点，从而防止 C 型失活。其次，即使在复极化后，它也能保持通道的激活门打开，从而允许长时间发生 C 型失活。
Voltage-activated K+ currents and their inactivation properties are important for controlling frequency-dependent signaling in neurons and other excitable cells. Two distinct molecular mechanisms for K+ channel inactivation have been described: N-type, which involves rapid occlusion of the open channel by an intracellular tethered blocker, and C-type, which involves a slower change at the extracellular mouth of the pore. We find that frequency-dependent cumulative inactivation of Shaker channels is very sensitive to changes of extracellular [K+] in the physiological range, with much more inactivation at low [K+](out), and that it results from the interaction of N- and C-type inactivation. N-type inactivation enhances C-type inactivation by two mechanisms. First, it inhibits outward K+ flux, which normally fills an external ion site and thus prevents C-type inactivation. Second, it keeps the channel's activation gate open even after repolarization, allowing C-type inactivation to occur for a prolonged period.