Research ArticleNEUROSCIENCE

Antiarrhythmics cure brain arrhythmia: The imperativeness of subthalamic ERG K+ channels in parkinsonian discharges

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Science Advances  10 May 2017:
Vol. 3, no. 5, e1602272
DOI: 10.1126/sciadv.1602272

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Abstract

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.”

Keywords
  • antiarrhythmics
  • brain rhythm disorders
  • burst discharge
  • ERG channels
  • Parkinson’s disease
  • subthalamic nucleus

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