Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan.
Taiwan Mouse Clinic - National Comprehensive Mouse Phenotyping and Drug Testing Center, Taipei, Taiwan.
Adv Exp Med Biol. 2018;1099:37-47. doi: 10.1007/978-981-13-1756-9_4.
Acid-sensing ion channels (ASICs) are a group of proton-gated ion channels belonging to the degenerin/epithelial sodium channel (DED/ENaC) family. There are at least six ASIC subtypes - ASIC1a, ASIC1b, ASIC2a, ASIC2b, ASIC3, and ASIC4 - all expressed in somatosensory neurons. ASIC3 is the most abundant in dorsal root ganglia (DRG) and the most sensitive to extracellular acidification. ASICs were found as the major player involved in acid-induced pain in humans. Accumulating evidence has further shown ASIC3 as the molecular determinant involved in pain-associated tissue acidosis in rodent models. Besides having a role in nociception, members of the DEG/ENaC family have been demonstrated as essential mechanotransducers in the nematode Caenorhabditis elegans and fly Drosophila melanogaster. ASICs are mammalian homologues of DEG/ENaC and therefore may play a role in mechanotransduction. However, the role of ASICs in neurosensory mechanotransduction is disputed. Here we review recent studies to probe the roles of ASICs in acid nociception and neurosensory mechanotransduction. In reviewing genetic models and delicate electrophysiology approaches, we show ASIC3 as a dual-function protein for both acid-sensing and mechano-sensing in somatosensory nerves and therefore involved in regulating both nociception and proprioception.
酸敏离子通道（ASICs）是一组质子门控离子通道，属于退行/上皮钠离子通道（DED/ENaC）家族。至少有六种 ASIC 亚型 - ASIC1a、ASIC1b、ASIC2a、ASIC2b、ASIC3 和 ASIC4 - 都在感觉神经元中表达。ASIC3 在背根神经节（DRG）中最为丰富，对细胞外酸化最敏感。ASICs 被发现是人类酸诱导疼痛的主要参与者。越来越多的证据进一步表明，ASIC3 是参与啮齿动物模型中与疼痛相关的组织酸中毒的分子决定因素。除了在伤害感受中发挥作用外，DEG/ENaC 家族的成员已被证明是线虫秀丽隐杆线虫和果蝇黑腹果蝇中的必需机械转导器。ASICs 是哺乳动物 DEG/ENaC 的同源物，因此可能在机械转导中发挥作用。然而，ASICs 在神经感觉机械转导中的作用存在争议。在这里，我们回顾了最近的研究，以探讨 ASICs 在酸敏性疼痛和神经感觉机械转导中的作用。在回顾遗传模型和精细的电生理学方法时，我们表明 ASIC3 作为感觉神经中的酸感应和机械感应的双重功能蛋白，因此参与调节伤害感受和本体感受。
