STATE-DEPENDENT INACTIVATION OF THE KV3 POTASSIUM CHANNEL
STATE-DEPENDENT INACTIVATION OF THE KV3 POTASSIUM CHANNEL
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DOI：
10.1016/s0006-3495(94)80517-x
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发表时间：
1994-08-01
影响因子：
3.4
通讯作者：
LEVITAN, IB
中科院分区：
文献类型：
--
作者：
MAROM, S;LEVITAN, IB
在非洲爪蟾卵母细胞表达系统中研究了Kv3（Kv1.3）延迟整流钾通道的失活。这些通道在一个长的去极化脉冲中振荡缓慢。此外，失活响应于一系列短去极化脉冲而累积（累积失活），尽管在每个短脉冲内没有显著的失活发生。累积失活的程度不依赖于去极化脉冲期间的电压，但它确实以双相方式作为脉冲间持续时间的函数而变化。此外，通过改变失活速率来影响累积失活速率。这些数据与Kv3通道失活是状态依赖性和电压无关性过程的模型一致。宏观和单通道实验表明，失活可以发生在通道开放之前的关闭（沉默）状态。也就是说，渠道不需要向客户开放。事实上，从沉默状态到失活状态的转变比在长去极化脉冲期间观察到的电流失活快几倍。长脉冲诱导的失活似乎是缓慢的，因为其速率受到通道处于开放状态而不是处于沉默状态的概率的限制，而通道可以从沉默状态恢复。外部钾和外部钙离子改变累积和长脉冲诱导的失活速率，表明拮抗性钾和钙结合步骤参与通道的正常门控。
Inactivation of Kv3 (Kv1.3) delayed rectifier potassium channels was studied in the Xenopus oocyte expression system. These channels inactivate slowly during a long depolarizing pulse. In addition, inactivation accumulates in response to a series of short depolarizing pulses (cumulative inactivation), although no significant inactivation occurs within each short pulse. The extent of cumulative inactivation does not depend on the voltage during the depolarizing pulse, but it does vary in a biphasic manner as a function of the interpulse duration. Furthermore, the rate of cumulative inactivation is influenced by changing the rate of deactivation. These data are consistent with a model in which Kv3 channel inactivation is a state-dependent and voltage-independent process. Macroscopic and single channel experiments indicate that inactivation can occur from a closed (silent) state before channel opening. That is, channels need not open to inactivate. The transition that leads to the inactivated state from the silent state is, in fact, severalfold faster then the observed inactivation of current during long depolarizing pulses. Long pulse-induced inactivation appears to be slow, because its rate is limited by the probability that channels are in the open state, rather than in the silent state from which they can inactivate. External potassium and external calcium ions alter the rates of cumulative and long pulse-induced inactivation, suggesting that antagonistic potassium and calcium binding steps are involved in the normal gating of the channel.