Burdakov Denis, Alexopoulos Haris, Vincent Angela, Ashcroft Frances M
Laboratory of Physiology, University of Oxford, Oxford, United Kingdom.
Eur J Neurosci. 2004 Dec;20(12):3281-5. doi: 10.1111/j.1460-9568.2004.03815.x.
The activity of hypothalamic neurons that release the neuropeptides orexin-A and orexin-B is essential for normal wakefulness. Orexin neurons fire spontaneously and are hyperpolarized and inhibited by physiological neuromodulators, but the intrinsic determinants of their electrical activity are poorly understood. We show that mouse orexin neurons coexpress orexin-A and orexin-B, and possess a low-voltage-activated A-type K(+) current (A-current) likely to be composed of Kv4.3 subunits. The A-current enhances the inhibitory influence of hyperpolarizing currents via two mechanisms: by delaying the resumption of spiking after hyperpolarization and by increasing the slope of the relation between the firing frequency and injected current. These results identify an important determinant of the firing dynamics of orexin neurons, and support the idea that the A-current can control neuronal gain.
释放神经肽食欲素-A和食欲素-B的下丘脑神经元活动对正常清醒至关重要。食欲素神经元自发放电,受到生理神经调质的超极化和抑制作用,但其电活动的内在决定因素却知之甚少。我们发现,小鼠食欲素神经元共表达食欲素-A和食欲素-B,并拥有一种可能由Kv4.3亚基组成的低电压激活A型钾电流(A电流)。A电流通过两种机制增强超极化电流的抑制作用:通过延迟超极化后放电的恢复以及通过增加放电频率与注入电流之间关系的斜率。这些结果确定了食欲素神经元放电动力学的一个重要决定因素,并支持A电流可以控制神经元增益的观点。