A SODIUM-CHANNEL GATING MODEL BASED ON SINGLE CHANNEL, MACROSCOPIC IONIC, AND GATING CURRENTS IN THE SQUID GIANT-AXON
A SODIUM-CHANNEL GATING MODEL BASED ON SINGLE CHANNEL, MACROSCOPIC IONIC, AND GATING CURRENTS IN THE SQUID GIANT-AXON
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DOI：
10.1016/s0006-3495(91)82186-5
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发表时间：
1991-12-01
影响因子：
3.4
通讯作者：
BEZANILLA, F
中科院分区：
文献类型：
--
作者：
VANDENBERG, CA;BEZANILLA, F
在没有二价阳离子的情况下，用马尔可夫模型拟合鱿鱼巨大轴突的电流来模拟钠通道的门控行为。利用单通道数据以最大似然准则选择最优模型，然后通过同时拟合宏观离子电流、ON和OFF门控电流以及宽电压范围内的单通道第一延迟密度来改进和扩展模型。最佳模型在通道打开之前具有五种关闭状态，至少从一种关闭状态和打开状态停止激活。正向活化速率常数随去极化而增大，失活速率常数随超极化而增大。从打开或关闭状态的失活速率通常比激活或失活速率慢，并且显示很少或没有电压依赖性。通道在失效之前往往会重新打开几次。宏观的激活和失活速率是由闭合、打开和失活状态转变的组合产生的。在负电位下，由于激活率比失活率慢，首次打开的时间支配着宏观电流：通道倾向于很少重新打开，并且通常在重新打开之前从关闭状态失活。在电位较高的情况下，首次打开的时间和爆发的持续时间共同产生宏观电流。
Sodium channel gating behavior was modeled with Markovian models fitted to currents from the cut-open squid giant axon in the absence of divalent cations. Optimum models were selected with maximum likelihood criteria using single-channel data, then models were refined and extended by simultaneous fitting of macroscopic ionic currents, ON and OFF gating currents, and single-channel first latency densities over a wide voltage range. Best models have five closed states before channel opening, with inactivation from at least one closed state as well as the open state. Forward activation rate constants increase with depolarization, and deactivation rate constants increase with hyperpolarization. Rates of inactivation from the open or closed states are generally slower than activation or deactivation rates and show little or no voltage dependence. Channels tend to reopen several times before inactivating. Macroscopic rates of activation and inactivation result from a combination of closed, open and inactivated state transitions. At negative potentials the time to first opening dominates the macroscopic current due to slow activation rates compared with deactivation rates: channels tend to reopen rarely, and often inactivate from closed states before they reopen. At more positive potentials, the time to first opening and burst duration together produce the macroscopic current.