Voltage-Gated Sodium Channels in Neocortical Pyramidal Neurons Display Cole-Moore Activation Kinetics.
Voltage-Gated Sodium Channels in Neocortical Pyramidal Neurons Display Cole-Moore Activation Kinetics.
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DOI：
10.3389/fncel.2018.00187
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发表时间：
2018
影响因子：
5.3
通讯作者：
Korngreen A
中科院分区：
文献类型：
--
作者：
Almog M;Barkai T;Lampert A;Korngreen A
探索动作电位的性质是更好地理解单个神经元和神经网络的计算性质的关键一步。电压门控钠通道是动作电位产生的关键因素。全面掌握这一通道的门控机制可以阐明动作电位产生的生物物理学。然而，电压门控钠通道的大多数模型假定协调的霍奇金和赫胥黎动力学门控方案。然而，目前尚不清楚霍奇金和赫胥黎模型是否适用于中枢神经系统神经元的动作电位模拟。为了解决这个问题，我们研究了电压门控钠通道的激活动力学。在这里，我们进行了高分辨率的电压钳实验，从大鼠脑片的第5层（L5）皮层锥体神经元的索马提取有核补丁。我们发现，门控机制不遵循传统的霍奇金和赫胥黎动力学和通道的电压依赖性很可能是由于快速关闭关闭转换，导致大量的起始潜伏期让人想起科尔-摩尔效应观察电压门控钾电导。因此，经典的Hodgkin和Huxley描述的钠通道动力学可能不适合模拟该通道的生理作用。此外，我们的结果调和明显矛盾的研究钠通道激活。我们的发现可能对钠通道在突触整合和动作电位产生中的作用具有关键意义。
Exploring the properties of action potentials is a crucial step toward a better understanding of the computational properties of single neurons and neural networks. The voltage-gated sodium channel is a key player in action potential generation. A comprehensive grasp of the gating mechanism of this channel can shed light on the biophysics of action potential generation. However, most models of voltage-gated sodium channels assume a concerted Hodgkin and Huxley kinetic gating scheme. However, it is not clear if Hodgkin and Huxley models are suitable for use in action potential simulations of central nervous system neurons. To resolve this, we investigated the activation kinetics of voltage-gated sodium channels. Here we performed high resolution voltage-clamp experiments from nucleated patches extracted from the soma of layer 5 (L5) cortical pyramidal neurons in rat brain slices. We show that the gating mechanism does not follow traditional Hodgkin and Huxley kinetics and that much of the channel voltage-dependence is probably due to rapid closed-closed transitions that lead to substantial onset latency reminiscent of the Cole-Moore effect observed in voltage-gated potassium conductances. Thus, the classical Hodgkin and Huxley description of sodium channel kinetics may be unsuitable for modeling the physiological role of this channel. Furthermore, our results reconcile between apparently contradicting studies sodium channel activation. Our findings may have key implications for the role of sodium channels in synaptic integration and action potential generation.
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影响因子：
5.5
作者：
Korngreen, A;Sakmann, B
通讯作者：
Sakmann, B
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