Acid-sensitive ion channels in gastrointestinal function.

Deviations from the physiological values of extracellular pH are monitored by multiple acid sensors. Acid-sensing ion channels are activated by moderate acidification, whereas transient receptor potential cation channels, notably TRPV1, are gated by severe acidosis. In contrast, ionotropic purinoceptor (P2X) ion channels, particularly P2X(2), and two-pore domain background K(+) channels, such as TASK, do not directly signal acidification but rather modulate cell membrane excitability in response to acidosis. These acid sensors, which are expressed by afferent neurons, are most relevant to the regulation of acid secretion, foregut motility and mucosal protection, as well as to gastrointestinal disturbances associated with inflammation, ischaemia and stasis.