Enomoto Akifumi, Han Juliette M, Hsiao Chie-Fang, Chandler Scott H
Department of Physiological Science, University of California, Los Angeles, California 90095, USA.
J Neurophysiol. 2007 Aug;98(2):710-9. doi: 10.1152/jn.00292.2007. Epub 2007 May 23.
Previous studies using pharmacological methods suggest that subthreshold sodium currents are critical for rhythmical burst generation in mesencephalic trigeminal neurons (Mes V). In this study, we characterized transient (I(NaT)), persistent (I(N)(aP)), and resurgent (I(res)) sodium currents in Na(v)1.6-null mice (med mouse, Na(v)1.6(-/-)) lacking expression of the sodium channel gene Scn8a. We found that peak transient, persistent, and resurgent sodium currents from med (Na(v)1.6(-/-)) mice were reduced by 18, 39, and 76% relative to their wild-type (Na(v)1.6(+/+)) littermates, respectively. Current clamp recordings indicated that, in response to sinusoidal constant amplitude current (ZAP function), all neurons exhibited membrane resonance. However, Mes V neurons from med mice had reduced peak amplitudes in the impedance-frequency relationship (resonant Q-value) and attenuated subthreshold oscillations despite the similar passive membrane properties compared with wild-type littermates. The spike frequency-current relationship exhibited reduced instantaneous discharge frequencies and spike block at low stimulus currents and seldom showed maintained spike discharge throughout the stimulus in the majority of med neurons compared with wild-type neurons. Importantly, med neurons never exhibited maintained stimulus-induced rhythmical burst discharge unlike those of wild-type littermates. The data showed that subthreshold sodium currents are critical determinants of Mes V electrogenesis and burst generation and suggest a role for resurgent sodium currents in control of spike discharge.
以往使用药理学方法的研究表明，阈下钠电流对于中脑三叉神经神经元（Mes V）的节律性爆发产生至关重要。在本研究中，我们对缺乏钠通道基因Scn8a表达的Na(v)1.6基因敲除小鼠（med小鼠，Na(v)1.6(-/-)）中的瞬时钠电流（I(NaT)）、持续性钠电流（I(NaP)）和复苏钠电流（I(res)）进行了表征。我们发现，与野生型（Na(v)1.6(+/+)）同窝小鼠相比，med（Na(v)1.6(-/-)）小鼠的峰值瞬时钠电流、持续性钠电流和复苏钠电流分别降低了18%、39%和76%。电流钳记录表明，在响应正弦恒定幅度电流（ZAP功能）时，所有神经元均表现出膜共振。然而，尽管与野生型同窝小鼠相比，med小鼠的Mes V神经元具有相似的被动膜特性，但其在阻抗-频率关系中的峰值幅度（共振Q值）降低，阈下振荡减弱。与野生型神经元相比，med神经元的动作电位频率-电流关系在低刺激电流下表现出瞬时放电频率降低和动作电位阻滞，并且在大多数med神经元中，在整个刺激过程中很少出现持续的动作电位放电。重要的是，与野生型同窝小鼠不同，med神经元从未表现出持续的刺激诱导节律性爆发放电。数据表明，阈下钠电流是Mes V电活动和爆发产生的关键决定因素，并提示复苏钠电流在控制动作电位放电中起作用。
