Roles of ASICs in nociception and proprioception

Abstract

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.