Graduate Institute of Biomedical Sciences, College of Medicine, Chang Gung University, Tao-Yuan, Taiwan.
Department of Biomedical Sciences, College of Medicine, Chang Gung University, Tao-Yuan, Taiwan.
Sci Adv. 2017 May 10;3(5):e1602272. doi: 10.1126/sciadv.1602272. eCollection 2017 May.
ERG K channels have long been known to play a crucial role in shaping cardiac action potentials and, thus, appropriate heart rhythms. The functional role of ERG channels in the central nervous system, however, remains elusive. We demonstrated that ERG channels exist in subthalamic neurons and have similar gating characteristics to those in the heart. ERG channels contribute crucially not only to the setting of membrane potential and, consequently, the firing modes, but also to the configuration of burst discharges and, consequently, the firing frequency and automaticity of the subthalamic neurons. Moreover, modulation of subthalamic discharges via ERG channels effectively modulates locomotor behaviors. ERG channel inhibitors ameliorate parkinsonian symptoms, whereas enhancers render normal animals hypokinetic. Thus, ERG K channels could be vital to the regulation of both cardiac and neuronal rhythms and may constitute an important pathophysiological basis and pharmacotherapeutic target for the growing list of neurological disorders related to "brain arrhythmias."
ERG K 通道长期以来一直被认为在塑造心脏动作电位方面起着至关重要的作用,从而维持适当的心律。然而,ERG 通道在中枢神经系统中的功能作用仍然难以捉摸。我们证明 ERG 通道存在于丘脑底核神经元中,并且其门控特性与心脏中的通道相似。ERG 通道不仅对膜电位的设定以及由此产生的发射模式至关重要,而且对爆发性放电的配置以及由此产生的丘脑底核神经元的发射频率和自动性也至关重要。此外,通过 ERG 通道调制丘脑底核放电可以有效地调节运动行为。ERG 通道抑制剂可改善帕金森病症状,而增强剂则使正常动物运动减少。因此,ERG K 通道对于心脏和神经元节律的调节可能至关重要,并且可能构成与“脑心律失常”相关的越来越多的神经紊乱的重要病理生理学基础和药物治疗靶标。