Acid-sensing ion channels 1a (ASIC1a) inhibit neuromuscular transmission in female mice.
Acid-sensing ion channels 1a (ASIC1a) inhibit neuromuscular transmission in female mice.
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DOI：
10.1152/ajpcell.00301.2013
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发表时间：
2014-02-15
期刊：
影响因子：
--
通讯作者：
Uchitel OD
中科院分区：
文献类型：
--
作者：
Urbano FJ;Lino NG;González-Inchauspe CM;González LE;Colettis N;Vattino LG;Wunsch AM;Wemmie JA;Uchitel OD
酸敏感离子通道（ASIC）开放响应细胞外酸中毒。ASIC1a是这些通道的一个特殊亚型，已被描述为在大脑中具有突触后分布，不仅与缺血和癫痫有关，而且与恐惧和精神疾病有关。高频刺激骨骼运动神经末梢（mnt）可以诱导突触前pH值变化，并结合突触间隙酸化，已知会导致肌肉疲劳。在这里，我们研究了ASIC1a通道在神经肌肉传递中的作用。我们将行为吊丝试验与电生理学、药理学和免疫荧光技术相结合，比较野生型和缺乏ASIC1a的小鼠（ASIC1a−/−敲除）。结果表明：1)ASIC1a−/−雌性小鼠比野生型弱，吊丝时间短；2) ASIC1a激活减少了自发性神经递质释放，表明这些通道位于单个mnt的突触前位置；3)通过细胞外局部应用酸性盐水溶液（pH = 6.0， HEPES/ mess为基础的溶液）模拟asic1a介导的作用；4)免疫荧光技术显示mnt上存在ASIC1a抗原。这些结果提示ASIC1a通道可能参与控制雌性小鼠的神经肌肉传递、肌肉收缩和疲劳。
Acid-sensing ion channels (ASIC) open in response to extracellular acidosis. ASIC1a, a particular subtype of these channels, has been described to have a postsynaptic distribution in the brain, being involved not only in ischemia and epilepsy, but also in fear and psychiatric pathologies. High-frequency stimulation of skeletal motor nerve terminals (MNTs) can induce presynaptic pH changes in combination with an acidification of the synaptic cleft, known to contribute to muscle fatigue. Here, we studied the role of ASIC1a channels on neuromuscular transmission. We combined a behavioral wire hanging test with electrophysiology, pharmacological, and immunofluorescence techniques to compare wild-type and ASIC1a lacking mice (ASIC1a −/− knockout). Our results showed that 1) ASIC1a −/− female mice were weaker than wild type, presenting shorter times during the wire hanging test; 2) spontaneous neurotransmitter release was reduced by ASIC1a activation, suggesting a presynaptic location of these channels at individual MNTs; 3) ASIC1a-mediated effects were emulated by extracellular local application of acid saline solutions (pH = 6.0; HEPES/MES-based solution); and 4) immunofluorescence techniques revealed the presence of ASIC1a antigens on MNTs. These results suggest that ASIC1a channels might be involved in controlling neuromuscular transmission, muscle contraction and fatigue in female mice.
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