1. Institut de Pharmacologie Moléculaire et Cellulaire, CNRS, 660 route des Lucioles, Sophia Antipolis, Valbonne 06560, France
2. ^*These authors contributed equally to this work

Abstract

Acid-sensing is associated with both nociception¹ and taste transduction². Stimulation of sensory neurons by acid is of particular interest, because acidosis accompanies many painful inflammatory and ischaemic conditions. The pain caused by acids is thought to be mediated by H⁺-gated cation channels present in sensory neurons^3–5. We have now cloned a H⁺-gated channel (ASIC, for acid-sensing ionic channel) that belongs to the amilor-ide-sensitive Na⁺ channe^l6–1 Vdegenerin^12–14 family of ion channels. Heterologous expression of ASIC induces an amiloride-sensitive cation (Na⁺ Ca²⁺ K⁺) channel which is transiently activated by rapid extracellular acidification. The biophysical and pharmacological properties of the ASIC channel closely match the H⁺-gated cation channel described in sensory neurons^3,15,16. ASIC is expressed in dorsal root ganglia and is also distributed widely throughout the brain. ASIC appears to be the simplest of ligand-gated channels.