Xu Xue-Feng, Tsai Hao-Jan, Li Lin, Chen Yi-Fan, Zhang Cheng, Wang Guang-Fa
Department of Pulmonary Medicine and Central Laboratory of Peking University First Hospital, Beijing 100034, China.
Sheng Li Xue Bao. 2009 Aug 25;61(4):305-16.
The cloned TWIK-related acid-sensitive K(+) channel (TASK-1) is sensitive to the pH changes within physiological pH range (pK~7.4). Recently, the native TASK-1-like channel was suggested to be the main contributor to the background (or leak) K(+) conductance in the motoneurons of the brain stem. Serotonin (5-HT) and variation of pH value in perfused solution could modulate these currents. Here we aimed to examine the properties and modulation of the currents by serotonin or variation of pH value in hypoglossal motoneurons of rats. Transverse slices were prepared from the brainstem of neonatal Sprague-Dawley rats (postnatal days 7-8). Hypoglossal motoneurons were used for the study. The leak K(+) current (TASK-1-like current) and hyperpolarization-activated cationic current (I(h)) were recorded with the whole-cell patch-clamp technique. The results showed that these currents were inhibited by acidified artificial cerebrospinal fluid (ACSF, pH 6.0) and activated by alkalized ACSF (pH 8.5). 5-HT (10 mumol/L) significantly inhibited both leak K(+) current and I(h) with depolarization of membrane potential and the occurrence of oscillation and/or spikes. Bath application of Ketanserine, an antagonist of 5-HT₂ receptor, reversed or reduced the inhibitory effect of acidified solution on leak K(+) current and I(h). The results suggest that 5-HT₂ receptors mediate the effects of acidified media on leak K(+) current and I(h) in hypoglossal motoneurons.
克隆的TWIK相关酸敏感钾通道（TASK-1）在生理pH范围内（pK~7.4）对pH变化敏感。最近，有研究表明，天然的TASK-1样通道是脑干运动神经元背景（或泄漏）钾电导的主要贡献者。血清素（5-HT）和灌注溶液中pH值的变化可以调节这些电流。在这里，我们旨在研究血清素或pH值变化对大鼠舌下运动神经元电流的特性和调节作用。从新生Sprague-Dawley大鼠（出生后7-8天）的脑干制备横向切片。舌下运动神经元用于该研究。采用全细胞膜片钳技术记录泄漏钾电流（TASK-1样电流）和超极化激活阳离子电流（I(h)）。结果表明，这些电流受到酸化人工脑脊液（ACSF，pH 6.0）的抑制，并被碱化ACSF（pH 8.5）激活。5-HT（10 μmol/L）显著抑制泄漏钾电流和I(h)，同时伴有膜电位去极化以及振荡和/或尖峰的出现。浴用5-HT₂受体拮抗剂酮色林可逆转或降低酸化溶液对泄漏钾电流和I(h)的抑制作用。结果表明，5-HT₂受体介导了酸化介质对舌下运动神经元泄漏钾电流和I(h)的影响。
