Baranauskas Gytis, Martina Marco
Psychiatric Institute, University of Illinois, Chicago, Illinois 60612, USA.
J Neurosci. 2006 Jan 11;26(2):671-84. doi: 10.1523/JNEUROSCI.2283-05.2006.
Hodgkin and Huxley established that sodium currents in the squid giant axons activate after a delay, which is explained by the model of a channel with three identical independent gates that all have to open before the channel can pass current (the HH model). It is assumed that this model can adequately describe the sodium current activation time course in all mammalian central neurons, although there is no experimental evidence to support such a conjecture. We performed high temporal resolution studies of sodium currents gating in three types of central neurons. The results show that, within the tested voltage range from -55 to -35 mV, in all of these neurons, the activation time course of the current could be fit, after a brief delay, with a monoexponential function. The duration of delay from the start of the voltage command to the start of the extrapolated monoexponential fit was much smaller than predicted by the HH model. For example, in prefrontal cortex pyramidal neurons, at -46 mV and 12 degrees C, the observed average delay was 140 micros versus the 740 micros predicted by the two-gate HH model and the 1180 micros predicted by the three-gate HH model. These results can be explained by a model with two closed states and one open state. In this model, the transition between two closed states is approximately five times faster than the transition between the second closed state and the open state. This model captures all major properties of the sodium current activation. In addition, the proposed model reproduces the observed action potential shape more accurately than the traditional HH model.
霍奇金和赫胥黎证实，鱿鱼巨轴突中的钠电流在延迟后激活，这可以用一个具有三个相同独立门控的通道模型来解释，即所有门控都必须打开，通道才能通过电流（HH模型）。据推测，该模型能够充分描述所有哺乳动物中枢神经元中钠电流的激活时间进程，尽管尚无实验证据支持这一推测。我们对三种类型的中枢神经元的钠电流门控进行了高时间分辨率研究。结果表明，在测试的从-55到-35 mV的电压范围内，所有这些神经元中的电流激活时间进程在短暂延迟后都可以用单指数函数拟合。从电压指令开始到外推单指数拟合开始的延迟持续时间远小于HH模型的预测值。例如，在-46 mV和12摄氏度下的前额叶皮层锥体神经元中，观察到的平均延迟为140微秒，而双门控HH模型预测为740微秒，三门控HH模型预测为1180微秒。这些结果可以用一个具有两个关闭状态和一个开放状态的模型来解释。在这个模型中，两个关闭状态之间的转换速度大约比第二个关闭状态与开放状态之间的转换速度快五倍。该模型捕捉了钠电流激活的所有主要特性。此外，所提出的模型比传统的HH模型更准确地再现了观察到的动作电位形状。
