Li Q Q, Wan K X, Xu M S, Wang L M, Zhang Y Y, Wang C T, Mao F X, Zhu J L, Pan Z M, Gao R
Department of Basic Medical Sciences, School of Medical, Shihezi University, Shihezi, 832000 China.
State Key Laboratory of Sheep Genetic Improvement and Healthy Production, Xinjiang Academy of Agricultural and Reclamation Sciences, Shihezi, 832000 China.
Mol Biol (Mosk). 2020 May-Jun;54(3):457-468. doi: 10.31857/S0026898420030106.
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 chemo-reception 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.
TWIK相关酸敏感钾通道1(TASK-1)是一种对细胞外质子敏感的“渗漏”钾通道。它有助于设定哺乳动物神经元的静息电位。TASK-1通道在中枢神经系统中与呼吸相关的神经元中广泛表达。细胞外酸中毒对TASK-1的抑制作用可使这些细胞去极化并增加其兴奋性。在此,我们描述了TASK-1在大鼠脑干中的分布,并表明TASK-1 mRNA存在于延髓腹外侧与呼吸相关的核团中,这些核团被认为是大鼠中枢化学感受的神经基础。吸入8%二氧化碳30分钟和60分钟后,阳性表达神经元中的TASK-1 mRNA水平显著上调。向大鼠侧脑室内注射TASK-1阻滞剂花生四烯乙醇胺(AEA),在治疗后10分钟时显示出明显的呼吸兴奋,吸气和呼气持续时间显著缩短,呼吸频率增加。我们认为,TASK-1通道可能作为中枢呼吸的化学感受器,并可能促成对pH敏感的呼吸效应。TASK-1通道可能是脑干中几个与呼吸相关核团中感受H⁺/CO₂的一个有吸引力的候选者。TASK-1很可能在生理和病理条件下参与呼吸中枢对pH敏感的化学调节。