A proton‐independent function of ASIC in Ciona intestinalis

Abstract

Acid‐Sensitive Ion Channels (ASICs) are neuronal‐specific voltage‐insensitive sodium channels gated by extracellular protons. ASIC functions in mammals include nociception, mechanosensation and modulation of synaptic transmission. However, the answer to what role protons play in mediating the effects of ASIC remains elusive. In this work we have examined ASIC from the ascidian Ciona intestinalis: a simple chordate organism with larval nervous system highly similar to the one of higher vertebrates. We show that Ciona has a single ASIC gene that gives rise to two spliced forms. CiASIC is expressed in most neurons of the larva, but absent in the adult nervous system. Despite sequence similarity with mammalian ASICs, CiASIC is proton‐insensitive when examined in heterologous systems or in larval neurons; the latter rules out the possibility that proton‐sensitivity is conferred by particular factors present only in Ciona neurons. Downregulation of CiASIC transcript by dsRNA disrupted the regular pattern of larval swimming, implying that proton‐independent mechanisms mediate the effects of ASIC in vivo. Together the data identify ASIC as a channel distinctive of chordate nervous system, and show that protons are not essential for ASIC function.This work was supported by NIH RO1DK054062.06A1 and AHA GIA grants to CC, NIH/NICHD R01HD050704 to ADG and APS Postdoctoral Fellowship in Physiological Genomics to TC.