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

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."

SUBMITTER: Huang CS

PROVIDER: S-EPMC5425237 | biostudies-literature | 2017 May

REPOSITORIES: biostudies-literature

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Antiarrhythmics cure brain arrhythmia: The imperativeness of subthalamic ERG K<sup>+</sup> channels in parkinsonian discharges.

Huang Chen-Syuan CS Wang Guan-Hsun GH Tai Chun-Hwei CH Hu Chun-Chang CC Yang Ya-Chin YC

Science advances 20170510 5

ERG K<sup>+</sup> 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 co ...[more]

PMID: 28508055

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Project description:The parkinsonian gait disorder and freezing of gait are therapeutically demanding symptoms with considerable impact on quality of life. The aim of this study was to assess the role of subthalamic and nigral neurons in the parkinsonian gait control using intraoperative microelectrode recordings of basal ganglia neurons during a supine stepping task. Twelve male patients (56 ± 7 years) suffering from moderate idiopathic Parkinson's disease (disease duration 10 ± 3 years, Hoehn and Yahr stage 2), undergoing awake neurosurgery for deep brain stimulation, participated in the study. After 10 s resting, stepping at self-paced speed for 35 s was followed by short intervals of stepping in response to random 'start' and 'stop' cues. Single- and multi-unit activity was analysed offline in relation to different aspects of the stepping task (attentional 'start' and 'stop' cues, heel strikes, stepping irregularities) in terms of firing frequency, firing pattern and oscillatory activity. Subthalamic nucleus and substantia nigra neurons responded to different aspects of the stepping task. Of the subthalamic nucleus neurons, 24% exhibited movement-related activity modulation as an increase of the firing rate, suggesting a predominant role of the subthalamic nucleus in motor aspects of the task, while 8% of subthalamic nucleus neurons showed a modulation in response to the attentional cues. In contrast, responsive substantia nigra neurons showed activity changes exclusively associated with attentional aspects of the stepping task (15%). The firing pattern of subthalamic nucleus neurons revealed gait-related firing regularization and a drop of beta oscillations during the stepping performance. During freezing episodes instead, there was a rise of beta oscillatory activity. This study shows for the first time specific, task-related subthalamic nucleus and substantia nigra single-unit activity changes during gait-like movements in humans with differential roles in motor and attentional control of gait. The emergence of perturbed firing patterns in the subthalamic nucleus indicates a disrupted information transfer within the gait network, resulting in freezing of gait.

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

Publications

Antiarrhythmics cure brain arrhythmia: The imperativeness of subthalamic ERG K<sup>+</sup> channels in parkinsonian discharges.

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

Publications

Antiarrhythmics cure brain arrhythmia: The imperativeness of subthalamic ERG K<sup>+</sup> channels in parkinsonian discharges.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets

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