Proton-gated cation channels--neuronal acid sensors in the central and peripheral nervous system

Metabolic hyperactivity or limited oxygen supply can cause a decrease of tissue pH. Severe tissue acidosis that accompanies ischemia and most forms of inflammation is painful and sensory neurons respond to acidic tissue pH with increased firing. H+-gated cation channels in sensory nerve endings are thought to be responsible for the activation of nociceptive afferents by acid. The members of one family of recently identified H+-gated cation channels (ASICs, Acid Sensing Ion Channels) are candidates for the acid sensor in sensory nerve endings. Certain ASIC subunits are also or exclusively expressed in neurons of the central nervous system (CNS) where the role of those cation channels is as for yet unknown. Neuronal activity is accompanied by pH fluctuations and the widespread expression of ASIC channels throughout the CNS suggests that activation of those ion channels by local acidic transients might play a role in neurotransmission or neuromodulation.