Harvard Medical School, Department of Neurobiology, 220 Longwood Avenue, Boston, MA 02115, USA.
J Neurophysiol. 2011 Feb;105(2):860-71. doi: 10.1152/jn.01056.2010. Epub 2010 Dec 15.
Purkinje neurons can spike very rapidly for sustained periods. We examined the cycle of sodium channel gating during high-frequency firing of Purkinje neurons, focusing on the kinetics of sodium channel inactivation and recovery during and after spikes. To analyze sodium channel availability during spiking, we recorded the firing patterns of acutely dissociated Purkinje neurons in current clamp and used these records as command voltages in voltage-clamp experiments in the same cell, adding step depolarizations at various points to assay availability. Sodium channel availability decreased abruptly during the spike, as expected, but never reached zero. During spontaneous firing (∼ 40 Hz at 37°C), availability decreased from nearly 90% before the spike to about 10-20% after the spike. With fast steady firing stimulated by current injection (∼ 300 Hz at 37°C), the availability decreased from about 60% between spikes to roughly 15-20% after the spike. Thus even at the fastest firing rates, sodium channel inactivation is incomplete after a spike, leaving a substantial fraction of sodium channels immediately available for activation. Also, inactivation recovered quickly during the early interspike interval (time constant ∼ 1 ms at 37°C), but developed slowly during the depolarization of the late interspike interval, ensuring high availability until spike threshold. These features of sodium channel gating, especially the availability remaining after the spike, reduce the refractory period and facilitate rapid repetitive firing.
浦肯野神经元可以持续快速地爆发。我们研究了浦肯野神经元高频放电时钠通道门控的循环，重点关注钠通道失活和恢复的动力学，包括在爆发期间和爆发后的动力学。为了分析爆发期间钠通道的可用性，我们在电流钳中记录急性分离的浦肯野神经元的放电模式，并将这些记录用作同一细胞中电压钳实验的指令电压，在不同点添加阶跃去极化以检测可用性。钠通道的可用性在爆发期间突然下降，如预期的那样，但从未降至零。在自发性放电（在 37°C 时约为 40Hz）期间，可用性从爆发前的近 90%下降到爆发后的 10-20%。在电流注入刺激的快速稳定放电（在 37°C 时约为 300Hz）下，可用性从两个爆发之间的约 60%下降到爆发后的大约 15-20%。因此，即使在最快的放电率下，钠通道失活在爆发后也不完全，留下相当一部分钠通道立即可用于激活。此外，失活在早期的爆发间期内迅速恢复（在 37°C 时的时间常数约为 1ms），但在晚期的爆发间期去极化期间恢复缓慢，确保在达到爆发阈值之前保持高的可用性。钠通道门控的这些特征，尤其是爆发后的可用性，缩短了不应期并促进了快速重复放电。
