AbbreviationsASICacid‐sensing ion channelGMQ2‐guanidine‐4‐methylquinazolineIntroductionAcid‐sensing ion channels (ASICs) belong to the degenerin/epithelial Na+ channel superfamily (Kellenberger and Schild, ). The six identified ASIC subunits (ASIC1a, ASIC1b, ASIC2a, ASIC2b, ASIC3 and ASIC4) encoded by four genes (ACCN1–ACCN4) (Wemmie et al., ) can form homotrimeric or heterotrimeric cation‐selective ion channels (Benson et al., ; Askwith et al., ; Sherwood et al., ). ASIC1a, ASIC2a, ASIC2b and ASIC4 isoforms are found in the CNS (Akopian et al., ; Alvarez de la Rosa et al., ; Wemmie et al., ), while ASIC3 and ASIC1b isoforms are predominantly expressed in the peripheral nervous system (Chen et al., ; Babinski et al., ). ASICs are implicated in neurotransmission, synaptic plasticity, learning, ischaemia and neuronal cell death and contribute to perception of acid‐mediated inflammatory or post‐operative pain (Wemmie et al., , ; Xiong et al., ; Gao et al., ; Yagi et al., ; Friese et al., ; Deval et al., , ; Yen et al., ).ASIC subunits demonstrate high‐sequence conservation between different mammalian species (rat, mouse and human) and isoforms (rat isoforms show 45–80% sequence similarity). The crystal structure of chicken ASIC1 at 1.9 Å resolution showed that the three‐dimensional architecture of ASIC subunits form trimeric functional complexes.
British Journal of Pharmacology – Wiley
Published: Jan 1, 2018
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