Taste receptor cells detect gustatory stimuli using a complex arrangement of ion channels, G protein-coupled receptors, and signaling cascades. Sour and salty tastes are detected by ion channels in the rat. Using a combination of homology screening and functional expression approaches, we screened a rat circumvallate papilla cDNA library and identified acid-sensing ion channel-2a (ASIC2a) and ASIC2b as candidates for the rat sour-sensing channels. In situ hybridization and reverse transcription-polymerase chain reaction experiments revealed that ASIC2a and ASIC2b transcripts were localized in taste bud cells. Immunohistochemistry and immunoprecipitation also revealed that both subunits were expressed in a subset of taste cells and that some of the cells expressed ASIC2a/ASIC2b heteromeric assemblies. Electrophysiological studies demonstrated that stimulation of acetic acid produced larger ASIC2 currents than did hydrochloric acid at the same pH. ASIC2a/ ASIC2b channels generated maximal inward currents at pH