ERG voltage-gated K+ channels regulate excitability and discharge dynamics of the medial vestibular nucleus neurones

ERG voltage-gated K+ channels regulate excitability and discharge dynamics of the medial vestibular nucleus neurones
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DOI:
10.1113/jphysiol.2008.155762
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发表时间:
2008-10-15
影响因子:
5.5
通讯作者:
Pettorossi, Vito Enrico
Pettorossi, Vito Enrico
中科院分区:
医学1区
文献类型:
--
作者:
Pessia, Mauro;Servettini, Ilenio;Pettorossi, Vito Enrico

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前庭内侧核神经元(MVNn)的放电特性主要取决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发现,电压门控K(+)通道ERG1A、ERG1B、ERG2和ERG3在P10和P60小鼠前庭核内高度表达。通过在细胞外和全细胞膜片钳研究中分析自发放电和对方形、斜坡和正弦样细胞内直流电注入的响应,从体外电生理学角度研究了这些通道在MVNn的尖峰产生机制和时间信息处理中的作用。我们发现超过一半的MVNn对ERG通道阻塞有反应(WAY-123,398, E4031),表现出自发活动和放电不规则性的增加。ERG阻滞对阶跃和斜坡电流注入的响应也有所改善,表现为第一峰潜伏期减少,放电速率增强,慢峰频率适应过程减少。ERG通道影响穗间斜率,但不影响穗形。此外,在响应类正弦电流时,ERG通道阻塞引起频率相关增益增强和相超前移位。综上所述,这些数据表明,ERG通道控制着MVNn的兴奋性、放电规律和共振特性。
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.