Inactivation and recovery of sodium currents in cerebellar Purkinje neurons: Evidence for two mechanisms
Inactivation and recovery of sodium currents in cerebellar Purkinje neurons: Evidence for two mechanisms
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DOI：
10.1016/s0006-3495(01)76052-3
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发表时间：
2001-02-01
影响因子：
3.4
通讯作者：
Bean, BP
中科院分区：
文献类型：
--
作者：
Raman, IM;Bean, BP
我们研究了小脑浦肯野神经元的电压依赖性钠电流的动力学，使用分离的神经元的全细胞记录，与其他细胞中的钠电流不同，浦肯野神经元失活的恢复伴随着相当大的离子电流。此外，恢复的程度和速度明显取决于产生失活的预脉冲的电压和持续时间。在短暂的、大的去极化（例如，在+30 mV下5 ms）之后的恢复比在长的、较小的去极化（例如，在短暂、大的去极化后复极化至-40 mV时，复苏的钠电流上升和衰减与失活的部分非单调恢复平行。这些现象可以用一个模型来解释，该模型包含两种失活机制：一种常规机制，其中沟道在没有传导电流的情况下恢复，以及第二种机制，其受到短暂的大的去极化的青睐，其中沟道通过短暂地经过打开状态而恢复，第二种机制与电压依赖性通道阻断一致，即只有当通道开放时，颗粒才能进入和离开通道。在从这种阻断状态恢复期间流动的钠电流可以在动作电位之后立即使细胞去极化，促进浦肯野神经元典型的高频放电。
We examined the kinetics of voltage-dependent sodium currents in cerebellar Purkinje neurons using whole-cell recording from dissociated neurons, Unlike sodium currents in other cells, recovery from inactivation in Purkinje neurons is accompanied by a sizeable ionic current. Additionally, the extent and speed of recovery depend markedly on the voltage and duration of the prepulse that produces inactivation. Recovery is faster after brief, large depolarizations (e.g,, 5 ms at +30 mV) than after long, smaller depolarizations (e.g., 100 ms at -30 mV), On repolarization to -40 mV following brief, large depolarizations, a resurgent sodium current rises and decays in parallel with partial, nonmonotonic recovery from inactivation. These phenomena can be explained by a model that incorporates two mechanisms of inactivation: a conventional mechanism, from which channels recover without conducting current, and a second mechanism, favored by brief, large depolarizations, from which channels recover by passing transiently through the open state, The second mechanism is consistent with voltage-dependent block of channels by a particle that can enter and exit only when channels are open. The sodium current flowing during recovery from this blocked state may depolarize cells immediately after an action potential, promoting the high-frequency firing typical of Purkinje neurons.