Acid-sensing ion channels emerged over 600 MYA and are conserved throughout the deuterostomes

Acid-sensing ion channels (ASICs) are proton-gated ion channels broadly expressed in the vertebrate nervous system, converting decreased extracellular pH into excitatory sodium current. ASICs were previously thought to be a vertebrate-specific branch of the DEG/ENaC family, a broadly conserved but functionally diverse family of channels. Here, we provide phylogenetic and experimental evidence that ASICs are conserved throughout deuterostome animals, showing that ASICs evolved over 600 million years ago. We also provide evidence of ASIC expression in the central nervous system of the tunicate, Oikopleura dioica. Furthermore, by comparing broadly related ASICs, we identify key molecular determinants of proton sensitivity and establish that proton sensitivity of the ASIC4 isoform was lost in the mammalian lineage. Taken together, these results suggest that contributions of ASICs to neuronal function may also be conserved broadly in numerous animal phyla.酸敏感离子通道（Acid-sensing ion channels，ASICs）是一类质子门控离子通道，广泛表达于脊椎动物神经系统，可将细胞外pH降低转化为兴奋性钠电流。此前学界普遍认为，ASICs是DEG/ENaC通道家族的脊椎动物特异性分支，该家族广泛保守但功能多样。本研究通过系统发育与实验证据证实，ASICs广泛保守于后口动物类群中，其演化起源可追溯至6亿年前。本研究同时提供了ASICs在被囊动物住囊虫（Oikopleura dioica）中枢神经系统中表达的证据。此外，通过比对不同类群的同源ASICs，我们鉴定出质子敏感性的关键分子决定簇，并证实ASIC4亚型的质子敏感性在哺乳动物谱系中发生了丢失。综上，本研究结果提示，ASICs对神经元功能的调控作用可能在众多动物门类中广泛保守。