TETRAETHYLAMMONIUM BLOCKADE DISTINGUISHES 2 INACTIVATION MECHANISMS IN VOLTAGE-ACTIVATED K+ CHANNELS
TETRAETHYLAMMONIUM BLOCKADE DISTINGUISHES 2 INACTIVATION MECHANISMS IN VOLTAGE-ACTIVATED K+ CHANNELS
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DOI：
10.1073/pnas.88.12.5092
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发表时间：
1991-06-01
影响因子：
11.1
通讯作者：
YELLEN, G
中科院分区：
文献类型：
--
作者：
CHOI, KL;ALDRICH, RW;YELLEN, G
电压激活的 K+ 通道是一系列密切相关的膜蛋白，它们的门控行为、电导和药理学各不相同。 K+ 通道之间的一个显着且生理上重要的差异是它们的失活率。失活速率从毫秒到秒不等，不同失活特性的K+通道对神经元的信号整合和重复放电特性的影响截然不同。克隆的 Shaker B (H4) 钾通道是 K+ 通道的一个例子，它会在几毫秒内失活。最近的实验表明，通过定点删除去除 Shaker 蛋白的 N 端区域实际上消除了这种快速失活，但修饰后的通道在持续数秒的长时间去极化过程中仍然失活。在这里，我们报告说，这种残余失活必须通过与野生型 Shaker 通道快速失活不同的机制发生。就像另一个 K+ 通道的失活一样 [Grissmer, S. & Calahan, M. (1989) Biophys。 J. 55, 203-206]，通过在通道的细胞外侧应用通道阻断剂四乙铵来延缓这种缓慢的失活。相比之下，野生型 Shaker 通道的快速失活仅对细胞内应用四乙铵敏感。细胞内的四乙铵减缓了快速失活过程，就好像它与失活颗粒的结合竞争一样。
Voltage-activated K+ channels are a family of closely related membrane proteins that differ in their gating behavior, conductance, and pharmacology. A prominent and physiologically important difference among K+ channels is their rate of inactivation. Inactivation rates range from milliseconds to seconds, and K+ channels with different inactivation properties have very different effects on signal integration and repetitive firing properties of neurons. The cloned Shaker B (H4) potassium channel is an example of a K+ channel that inactivates in a few milliseconds. Recent experiments have shown that removal of an N-terminal region of the Shaker protein by site-directed deletion practically abolishes this fast inactivation, but the modified channel does still inactivate during a prolonged depolarization lasting many seconds. Here we report that this remnant inactivation must occur by a distinct mechanism from the rapid inactivation of the wild-type Shaker channel. Like the inactivation of another K+ channel [Grissmer, S. & Calahan, M. (1989) Biophys. J. 55, 203-206], this slow inactivation is retarded by the application of a channel blocker, tetraethylammonium, to the extracellular side of the channel. By contrast, the fast inactivation of the wild-type Shaker channel is sensitive only to intracellular application of tetraethylammonium. Intracellular tetraethylammonium slows down the fast inactivation process, as though it competes with the binding of the inactivation particle.