ATP-Activated Channels in Excitable Cells

Abstract

There is increasing evidence that ATP may play a role as an extracellular chemical messenger, probably even a true neurotransmitter. The strongest evidence for ATP being used as a synaptic transmitter has come from studies on sympathetic transmission to smooth muscle targets in the vas deferens and various blood vessels. For example, ATP applied to rat or guinea pig vas deferens muscle depolarizes the muscle and produces a twitch like that elicited by nerve stimulation. Both the ATP-induced depolarization and the nerve-evoked excitatory junction potential can be inhibited by structural analogues of ATP like arylazido aminopropionyl ATP (ANAPP₃) and α,β-methylene ATP (Sneddon et al., 1982; Sneddon and Burnstock, 1984; Sneddon and Westfall, 1984). Recently, it has been shown that isolated vas deferens smooth muscle cells contain cation-selective channels that are opened by micromolar concentrations of ATP (Nakazawa and Matsuki, 1987; Friel, 1988). The channels have a reversal potential near 0 mV so that they have an excitatory effect on the cell. It seems very likely that a component of fast, nonadrenergic, noncholinergic transmission is mediated by nerve-released ATP opening these channels.