Acid‐Sensing Ion Channel 2 modulates the current properties and neuropeptide potentiation of proton‐gated currents

Abstract

Acid‐sensing ion channels (ASICs) are proton‐gated channels required for normal behavior and sensory transduction. ASICs may also play an important role in injuries where prolonged acidosis occurs including stroke and inflammation. The specific biophysical properties of ASIC channels are dependent on their subunit composition and the presence of modulatory compounds such as RFamide neuropeptides. ASIC2 subunits regulate ASIC1a current via the formation of heteromeric channels, but the specific properties modulated by these subunits are not entirely understood. In this study, we examined the biophysical properties of ASIC1/2 heteromeric channels expressed in Xenopus oocytes. We determined that ASIC response to RFamide neuropeptides is dramatically altered by the presence of ASIC2 subunits. Surprisingly, we found that steady‐state desensitization of both heteromeric and ASIC2a homomeric channels was inhibited by RFamide peptides. Furthermore, heteromeric channels were responsive to a larger number of peptides compared to ASIC1a homomultimers. Our data suggest that in addition to affecting primary current properties, the ASIC2 subunits may also confer enhanced peptide sensitivity to proton‐gated currents in vivo, which may be important for the physiological and pathological roles of ASICs.