Abstract

TWIK-related acid-sensitive potassium channel-1 (TASK-1) is a “leak” potassium channel sensitive to extracellular protons. It contributes to setting the resting potential in mammalian neurons. TASK-1 channels are widely expressed in respiratory-related neurons in the central nervous system. Inhibition of TASK-1 by extracellular acidosis can depolarize and increase the excitability of these cells. Here we describe the distribution of TASK-1 in the rat brainstem and show that TASK-1 mRNAs are present in respiratory-related nuclei in the ventrolateral medulla, which have been proposed as neural substrates for central chemoreception in rats. After inhalation of 8% CO₂ for 30 and 60 min, TASK-1 mRNA levels in positive-expression neurons were remarkably upregulated. Injection of the TASK-1 blocker anandamide (AEA) into the rat lateral cerebral ventricle, showed a significant excitement of respiratory at 10 min posttreatment, with a marked decrease in inspiratory and expiratory durations and an increased frequency of respiration. We suggest that TASK-1 channel may serve as a chemosensor for in central respiration and may contribute to pH-sensitive respiratory effects. TASK-1 channel might be an attractive candidate for sensing H⁺/CO₂ in several respiratory-related nuclei in the brainstem. It is likely that TASK-1 participates in pH-sensitive chemical regulation in the respiratory center under physiological and pathological conditions.

中文翻译：

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pH敏感钾通道TASK-1是用于大鼠中央呼吸调节的化学传感器。

摘要

TWIK相关的酸敏感钾通道1（TASK-1）是对细胞外质子敏感的“泄漏”钾通道。它有助于设定哺乳动物神经元的静息潜力。TASK-1通道在中枢神经系统的呼吸相关神经元中广泛表达。细胞外酸中毒对TASK-1的抑制作用可以使这些细胞去极化并增加其兴奋性。在这里，我们描述了TASK-1在大鼠脑干中的分布，并表明TASK-1 mRNA存在于腹侧延髓的呼吸相关核中，这已被提出作为大鼠中枢化学感受神经的底物。吸入8％CO _2后在30和60分钟时，阳性表达神经元中的TASK-1 mRNA水平显着上调。将TASK-1阻断剂anandamide（AEA）注入大鼠大脑侧脑室后，在治疗10分钟后，呼吸明显兴奋，吸气和呼气时间显着减少，呼吸频率增加。我们建议TASK-1通道可作为中央呼吸的化学传感器，并可能对pH敏感的呼吸作用有贡献。TASK-1通道可能是在脑干的几个呼吸相关核中感应H ⁺ / CO ₂的诱人候选物。TASK-1可能在生理和病理条件下参与了呼吸中枢对pH敏感的化学调节。