TASK-1 is a highly modulated pH-sensitive 'leak' K+ channel expressed in brainstem respiratory neurons
TASK-1 is a highly modulated pH-sensitive 'leak' K+ channel expressed in brainstem respiratory neurons
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DOI：
10.1016/s0034-5687(01)00288-2
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发表时间：
2001-12-01
期刊：
影响因子：
--
通讯作者：
Lei, QB
中科院分区：
文献类型：
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作者：
Bayliss, DA;Talley, EM;Lei, QB
中枢呼吸化学感受器在对大脑pH和/或PCO变化的稳态反应中调节呼吸动力(2)。多个脑干部位被认为是中枢化学接收的神经底物，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，我们描述了与克隆的大鼠TASK-1电流相同的动力学和电压依赖特性的K+电流。在与TASK-1相同的生理pH范围内，天然电流对酸碱变化敏感(pk类似于7.4)，而天然和克隆的pH敏感电流也同样受到神经递质和吸入麻醉剂的调节。这种pH敏感的TASK-1通道是一个很有吸引力的候选通道，因为它在呼吸相关神经元中有功能表达，包括呼吸道运动神经元和蓝斑(LC)的可能化学感受器神经元。胞外酸中毒抑制TASK-1通道可以使这些细胞去极化并增加兴奋性，从而有助于LC神经元的化学感受器功能，并直接增加呼吸运动神经元的输出。(C)2001 Elsevier Science B.V.保留所有权利。
Central respiratory chemoreceptors adjust respiratory drive in a homeostatic response to alterations in brain pH and/or Pco(2). 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 similar to 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. (C) 2001 Elsevier Science B.V. All rights reserved.