Acid-sensing ion channels (ASICs) in mouse skeletal muscle afferents are heteromers composed of ASIC1a, ASIC2, and ASIC3 subunits
Acid-sensing ion channels (ASICs) in mouse skeletal muscle afferents are heteromers composed of ASIC1a, ASIC2, and ASIC3 subunits
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DOI：
10.1096/fj.12-220400
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发表时间：
2013-02-01
期刊：
影响因子：
4.8
通讯作者：
Benson, Christopher J.
中科院分区：
文献类型：
--
作者：
Gautam, Mamta;Benson, Christopher J.
酸敏感离子通道（asic）在骨骼肌传入神经中表达，它们感知细胞外酸中毒和缺血和运动时释放的其他代谢物。asic是几种异构体（ASIC1a、ASIC1b、ASIC2a、ASIC2b和ASIC3）的同源三聚体或异源三聚体，每个通道显示不同的特性。为了解剖肌肉传入神经中ASIC的组成，我们使用全细胞膜片钳记录研究了野生型（C57BL/6J）和特异性ASIC（-/-）小鼠分离的标记小鼠肌肉传入神经的酸诱发电流特性（振幅、pH敏感性、脱敏和脱敏恢复动力学以及药理学调节）。我们发现野生型肌肉传入中asic样电流表现出快速脱敏，表明它们是由异质通道携带的。来自ASIC1a（-/-）肌肉传入的电流对ph值的敏感性较低，恢复速度更快；来自ASIC2（-/-）小鼠的电流表现出锌增强减弱；来自ASIC3（-/-）小鼠的电流表现出比野生型小鼠更慢的脱敏。最后，ASIC1a、ASIC2a和ASIC3缺失的三空小鼠中没有asic样电流。我们得出结论，ASIC1a、ASIC2a和ASIC3异构体是骨骼肌传入事件的主要通道。这些结果将有助于我们了解asic在运动生理学中的作用，并为潜在的药物治疗肌肉疼痛提供分子靶点。小鼠骨骼肌传入事件中的酸感离子通道（asic）是由ASIC1a、ASIC2和ASIC3亚基组成的异构体。中国生物医学工程学报，2013,32(2):481 - 481。www.fasebj.org
Acid-sensing ion channels (ASICs) are expressed in skeletal muscle afferents, in which they sense extracellular acidosis and other metabolites released during ischemia and exercise. ASICs are formed as homotrimers or heterotrimers of several isoforms (ASIC1a, ASIC1b, ASIC2a, ASIC2b, and ASIC3), with each channel displaying distinct properties. To dissect the ASIC composition in muscle afferents, we used whole-cell patch-clamp recordings to study the properties of acid-evoked currents (amplitude, pH sensitivity, the kinetics of desensitization and recovery from desensitization, and pharmacological modulation) in isolated, labeled mouse muscle afferents from wild-type (C57BL/6J) and specific ASIC(-/-) mice. We found that ASIC-like currents in wild-type muscle afferents displayed fast desensitization, indicating that they are carried by heteromeric channels. Currents from ASIC1a(-/-) muscle afferents were less pH-sensitive and displayed faster recovery, currents from ASIC2(-/-) mice showed diminished potentiation by zinc, and currents from ASIC3(-/-) mice displayed slower desensitization than those from wild-type mice. Finally, ASIC-like currents were absent from triple-null mice lacking ASIC1a, ASIC2a, and ASIC3. We conclude that ASIC1a, ASIC2a, and ASIC3 heteromers are the principle channels in skeletal muscle afferents. These results will help us understand the role of ASICs in exercise physiology and provide a molecular target for potential drug therapies to treat muscle pain.-Gautam, M., Benson, C. J. Acid-sensing ion channels (ASICs) in mouse skeletal muscle afferents are heteromers composed of ASIC1a, ASIC2, and ASIC3 subunits. FASEB J. 27, 793-802 (2013). www.fasebj.org