ATP-activated channels in excitable cells

Abstract

Extracellular ATP is an activator or modulator of ionic channels in a wide variety of excitable cells. There appears to be a class of related cation-permeable ATP-activated channels in skeletal muscle, cardiac muscle, smooth muscle, and neurons; the channels in the different cell types appear to be similar, but not identical, in their ionic selectivity, receptor selectivity, and pharmacology. In all cases, these channels reverse near 0 mV and activation by ATP produces an excitatory effect. Much remains to be learned about these channels, their possible existence and roles in other cell types, and their relation to other types of ligand-gated channels. It will be especially important to develop more specific pharmacological blockers (and activators) in order to distinguish subtypes and to assess their physiological role. Another type of channel, so far described only in cardiac atrial cells, is identical to the channels in cardiac atrial cells activated by ACh receptors; it will be interesting to see if this type of receptor-channel complex is also found in neurons or other cells. In a variety of cells, ATP also acts as a modulator of voltage-dependent channels and of channels activated by other transmitters. It seems very likely that more instances of such modulation will be described in years to come. Possible second-messenger pathways mediating such modulation remain to be elucidated.