TASK-1是一种在脑干呼吸神经元中表达的高度调节的ph敏感“泄漏”K+通道

Douglas A Bayliss, Edmund M Talley, Jay E Sirois, Qiubo Lei
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引用次数: 170

摘要

中枢呼吸化学感受器调节呼吸驱动对大脑pH值和/或二氧化碳分压变化的稳态反应。多个脑干部位被认为是中枢化学接受的神经底物,但呼吸神经元化学敏感性的分子底物尚未确定。在表达TASK-1转录本的大鼠脑干神经元中,一个双孔域K+通道,我们表征了K+电流具有与克隆大鼠TASK-1电流相同的动力学和电压依赖特性。原生电流在与TASK-1 (pK ~ 7.4)相同的生理pH范围内对酸碱变化敏感,并且原生电流和克隆的pH敏感电流被神经递质和吸入麻醉剂类似地调节。这种ph敏感的TASK-1通道是一种有吸引力的候选通道,可以介导化学接受,因为它在呼吸相关神经元中有功能表达,包括气道运动神经元和蓝斑(LC)的化学受体神经元。胞外酸中毒抑制TASK-1通道可使这些细胞去极化并增加兴奋性,从而促进LC神经元的化学受体功能,并直接增强呼吸运动神经元输出。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
TASK-1 is a highly modulated pH-sensitive ‘leak’ K+ channel expressed in brainstem respiratory neurons

Central respiratory chemoreceptors adjust respiratory drive in a homeostatic response to alterations in brain pH and/or PCO2. Multiple brainstem sites are proposed as neural substrates for central chemoreception, but molecular substrates that underlie chemosensitivity in respiratory neurons have not been identified. In rat brainstem neurons expressing transcripts for TASK-1, a two-pore domain K+ channel, we characterized K+ currents with kinetic and voltage-dependent properties identical to cloned rat TASK-1 currents. Native currents were sensitive to acid and alkaline shifts in the same physiological pH range as TASK-1 (pK∼7.4), and native and cloned pH-sensitive currents were modulated similarly by neurotransmitters and inhalational anesthetics. This pH-sensitive TASK-1 channel is an attractive candidate to mediate chemoreception because it is functionally expressed in respiratory-related neurons, including airway motoneurons and putative chemoreceptor neurons of locus coeruleus (LC). Inhibition of TASK-1 channels by extracellular acidosis can depolarize and increase excitability in those cells, thereby contributing to chemoreceptor function in LC neurons and directly enhancing respiratory motoneuronal output.

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