Pessia Mauro, Servettini Ilenio, Panichi Roberto, Guasti Leonardo, Grassi Silvarosa, Arcangeli Annarosa, Wanke Enzo, Pettorossi Vito Enrico
Department of Internal Medicine, Section of Human Physiology, University of Perugia, Perugia, Italy.
J Physiol. 2008 Oct 15;586(20):4877-90. doi: 10.1113/jphysiol.2008.155762. Epub 2008 Aug 21.
The discharge properties of the medial vestibular nucleus neurones (MVNn) critically depend on the activity of several ion channel types. In this study we show, immunohistochemically, that the voltage-gated K(+) channels ERG1A, ERG1B, ERG2 and ERG3 are highly expressed within the vestibular nuclei of P10 and P60 mice. The role played by these channels in the spike-generating mechanisms of the MVNn and in temporal information processing was investigated electrophysiologically from mouse brain slices, in vitro, by analysing the spontaneous discharge and the response to square-, ramp- and sinusoid-like intracellular DC current injections in extracellular and whole-cell patch-clamp studies. We show that more than half of the recorded MVNn were responsive to ERG channel block (WAY-123,398, E4031), displaying an increase in spontaneous activity and discharge irregularity. The response to step and ramp current injection was also modified by ERG block showing a reduction of first spike latency, enhancement of discharge rate and reduction of the slow spike-frequency adaptation process. ERG channels influence the interspike slope without affecting the spike shape. Moreover, in response to sinusoid-like current, ERG channel block caused frequency-dependent gain enhancement and phase-lead shift. Taken together, the data demonstrate that ERG channels control the excitability of MVNn, their discharge regularity and probably their resonance properties.
内侧前庭核神经元(MVNn)的放电特性严重依赖于几种离子通道类型的活性。在本研究中,我们通过免疫组织化学方法表明,电压门控钾通道ERG1A、ERG1B、ERG2和ERG3在P10和P60小鼠的前庭核中高度表达。通过在体外对小鼠脑片进行细胞外和全细胞膜片钳研究,分析自发放电以及对方形、斜坡形和正弦形细胞内直流电流注入的反应,从电生理学角度研究了这些通道在MVNn的动作电位产生机制和时间信息处理中的作用。我们发现,超过一半的记录到的MVNn对ERG通道阻断剂(WAY-123,398、E4031)有反应,表现出自发活动增加和放电不规则性。ERG通道阻断也改变了对阶跃和斜坡电流注入的反应,表现为首次动作电位潜伏期缩短、放电率增加以及慢动作电位频率适应过程减弱。ERG通道影响动作电位间期斜率,但不影响动作电位形状。此外,在对正弦形电流的反应中,ERG通道阻断导致频率依赖性增益增强和相位超前移位。综上所述,这些数据表明ERG通道控制着MVNn的兴奋性、它们的放电规律性以及可能的共振特性。