Multiple types of Na+ currents mediate action potential electrogenesis in small neurons of mouse dorsal root ganglia
Multiple types of Na+ currents mediate action potential electrogenesis in small neurons of mouse dorsal root ganglia
复制标题
DOI：
10.1007/s00424-006-0104-3
复制
发表时间：
2006-10-01
影响因子：
4.5
通讯作者：
Ogata, Nobukuni
中科院分区：
文献类型：
--
作者：
Matsutomi, Tomoya;Nakamoto, Chizumi;Ogata, Nobukuni
背根神经节（DRG）的小（直径< 25 μ m）神经元表达多种电压门控Na+通道亚型，其中两种对河豚毒素（TTX）具有抗性。每个亚型介导Na+电流具有不同的动力学性质。然而，目前尚不清楚每种类型的Na+通道如何促进小DRG神经元动作电位的产生。因此，我们利用野生型（WT）和Na(V)1.8敲除（KO）小鼠，研究了电压钳记录中Na+电流与电流钳记录中相应动作电位的相关性，以阐明DRG小神经元的动作电位生电。根据TTX敏感性和动力学特性，我们将小DRG神经元中的Na+电流分为TTX敏感(TTX- s)/快速Na+电流、TTX耐(TTX- r)/慢Na+电流和TTX-r /持续Na+电流三类。同一神经元的同时电压和电流钳记录显示，WT小DRG神经元的动作电位主要依赖于Na(V)1.8介导的TTX-R/慢Na+电流。令人惊讶的是，在WT小DRG神经元中，由于稳态失活的超极化移位（h(∞)），TTX-S/快速Na+电流的很大一部分被关闭，而在KO小DRG神经元中，缺乏TTX-R/慢Na+电流，TTX-S/快速Na+电流可能通过h向正方向的代偿移位产生动作电位。我们还证实了由Na(V)1.9介导的TTX-R/持续Na+电流实际上调节了小DRG神经元的阈下兴奋性。此外，我们还证明当TTX-R/持续Na+电流的振幅异常增加时，该电流可以携带动作电位。因此，我们的研究结果表明，小DRG神经元的动作电位是由多种机制共同产生和调节的，这些机制可能导致小DRG神经元具有独特的功能特性。
Small (< 25 mu m in diameter) neurons of the dorsal root ganglion (DRG) express multiple voltage-gated Na+ channel subtypes, two of which being resistant to tetrodotoxin (TTX). Each subtype mediates Na+ current with distinct kinetic property. However, it is not known how each type of Na+ channel contributes to the generation of action potentials in small DRG neurons. Therefore, we investigated the correlation between Na+ currents in voltage-clamp recordings and corresponding action potentials in current-clamp recordings, using wild-type (WT) and Na(V)1.8 knock-out (KO) mice, to clarify the action potential electrogenesis in small DRG neurons. We classified Na+ currents in small DRG neurons into three categories on the basis of TTX sensitivity and kinetic properties, i.e., TTX-sensitive (TTX-S)/fast Na+ current, TTX-resistant (TTX-R)/slow Na+ current, and TTX-R/persistent Na+ current. Our concurrent voltage- and current-clamp recordings from the same neuron revealed that the action potentials in WT small DRG neurons were mainly dependent on TTX-R/slow Na+ current mediated by Na(V)1.8. It was surprising that a large portion of TTX-S/fast Na+ current was switched off in WT small DRG neurons due to a hyperpolarizing shift of the steady-state inactivation (h(infinity)), whereas in KO small DRG neurons which are devoid of TTX-R/slow Na+ current, the action potentials were generated by TTX-S/fast Na+ current possibly through a compensatory shift of h. in the positive direction. We also confirmed that TTX-R/persistent Na+ current mediated by Na(V)1.9 actually regulates subthreshold excitability in small DRG neurons. In addition, we demonstrated that TTX-R/persistent Na+ current can carry an action potential when the amplitude of this current was abnormally increased. Thus, our results indicate that the action potentials in small DRG neurons are generated and regulated with a combination of multiple mechanisms that may give rise to unique functional properties of small DRG neurons.