Resurgent Na currents in four classes of neurons of the cerebellum
Resurgent Na currents in four classes of neurons of the cerebellum
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DOI：
10.1152/jn.00261.2004
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发表时间：
2004-11-01
影响因子：
2.5
通讯作者：
Raman, IM
中科院分区：
文献类型：
--
作者：
Afshari, FS;Ptak, K;Raman, IM
动作电位放电率通常受到不应期的限制，这取决于电压门控Na通道失活后的恢复。在小脑浦肯野神经元中，Na通道的动力学似乎专门用于快速放电。在去极化时，内源性开放通道阻断剂迅速终止电流，但阻止“快速”失活门的结合。在复极化时，阻断剂的解结合产生“复苏”Na电流，同时允许通道快速恢复。因为其他小脑神经元，包括颗粒细胞，单极刷细胞，小脑核的神经元，也快速发射，我们测试这些细胞是否也可能表达Na通道与复苏动力学。从小鼠和大鼠急性分离神经元，并在电压钳下记录TTX敏感的Na电流。与浦肯野细胞不同，其他小脑神经元在针对电压钳位Na电流优化的溶液中仅产生微小的复苏电流（50 mM Na+; Co2+替代Ca 2+）。然而，在更多的生理离子条件下（155 mM Na+; 2 mM Ca 2+与0.03 mM Cd 2+），颗粒细胞，单极刷状细胞和小脑核细胞都产生了强大的复苏电流。复苏电流的增加，这是大于预测的Goldman-Hodgkin-Katz方程，似乎是由于敲除的开放通道阻滞剂的渗透离子，以及救济的二价块在负电位的组合。这些结果表明，复苏电流是典型的许多小脑神经元，并建议，快速开放通道阻滞和解除阻滞可能是一个广泛的机制，恢复Na通道的可用性在快速放电神经元。
Action potential firing rates are generally limited by the refractory period, which depends on the recovery from inactivation of voltage-gated Na channels. In cerebellar Purkinje neurons, the kinetics of Na channels appear specialized for rapid firing. Upon depolarization, an endogenous open-channel blocker rapidly terminates current flow but prevents binding of the "fast" inactivation gate. Upon repolarization, unbinding of the blocker produces "resurgent" Na current while allowing channels to recover rapidly. Because other cerebellar neurons, including granule cells, unipolar brush cells, and neurons of the cerebellar nuclei, also fire rapidly, we tested whether these cells might also express Na channels with resurgent kinetics. Neurons were acutely isolated from mice and rats, and TTX-sensitive Na currents were recorded under voltage clamp. Unlike Purkinje cells, the other cerebellar neurons produced only tiny resurgent currents in solutions optimized for voltage-clamping Na currents (50 mM Na+; Co2+ substitution for Ca2+). Under more physiological ionic conditions (155 mM Na+; 2 mM Ca2+ with 0.03 mM Cd2+), however, granule cells, unipolar brush cells, and cerebellar nuclear cells all produced robust resurgent currents. The increase in resurgent current, which was greater than predicted by the Goldman-Hodgkin-Katz equation, appeared to result from a combination of knock-off of open-channel blockers by permeating ions as well as relief of divalent block at negative potentials. These results indicate that resurgent current is typical of many cerebellar neurons and suggest that rapid open-channel block and unblock may be a widespread mechanism for restoration of Na channel availability in rapidly firing neurons.