Acid-sensing ion channels (ASICs) are structurally related to epithelial sodium channel proteins. They are gated by protons, blocked by amiloride, and their transcripts are localized to sensory ganglia. Their pH sensitivity and distribution makes them interesting candidates to serve as primary transducers of local pH changes during ischemia or tissue injury to pain signals to the CNS. These channels can allow quite large and persistent inward currents in native sensory neurons that can cause sustained firing of action potentials that lead to pain perception. Using the rat ASIC3 sequence de Weille et al. cloned the human gene encoding ASIC3. During severe cardiac ischemia extracellular pH levels can drop as low as 6.7, and a study of eight different functional properties of large acid-gated currents in rat cardiac afferent neurons corresponded well to ASIC3 channels transfected into COS-7 cells.