Patil P G, Brody D L, Yue D T
Program in Molecular and Cellular Physiology, Department of Biomedical Engineering, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA.
Neuron. 1998 May;20(5):1027-38. doi: 10.1016/s0896-6273(00)80483-3.
We have investigated the inactivation mechanism of neuronal N-, P/Q-, and R-type calcium channels. Although channels inactivate slowly during square-pulse depolarization, as observed previously, we now find that they inactivate profoundly during a train of action potential (AP) waveforms. The apparent paradox arises from a voltage-dependent mechanism in which channels inactivate preferentially from intermediate closed states along the activation pathway. Inactivation can therefore extend beyond the brief duration of AP waveforms to continue between spikes, as the channel undergoes repetitive cycles of activation and deactivation. The extent of inactivation during a train is strongly affected by the subunit composition of channels. Preferential closed-state inactivation of neuronal calcium channels could produce widely variable depression of Ca2+ entry during a train of APs.
我们研究了神经元N型、P/Q型和R型钙通道的失活机制。尽管如先前观察到的那样，通道在方波去极化期间失活缓慢，但我们现在发现它们在一串动作电位（AP）波形期间会深度失活。这种明显的矛盾源于一种电压依赖性机制，即通道沿着激活途径优先从中间关闭状态失活。因此，失活可以延伸到AP波形的短暂持续时间之外，在尖峰之间继续，因为通道经历激活和失活的重复循环。一串动作电位期间的失活程度受到通道亚基组成的强烈影响。神经元钙通道优先的关闭状态失活可能在一串动作电位期间产生广泛变化的Ca2+内流抑制。
