Nanomolar concentrations of extracellular ATP activate membrane Ca channels in snail neurones

Abstract

Intracellular ATP is known to affect the electrical properties of membranes indirectly by acting intracellularly as a substrate for ATPases such as (Na⁺+K⁺)ATPase, Ca²⁺-ATPase or adenylate cyclase. More recently, extracellular ATP has been shown to act on effector cells innervated by autonomic nerves and a purinergic receptor hypothesis has been proposed for this effect^1,2. Extracellular ATP also acts on the slow inward current, I_si, of cardiac muscle membranes^3,4 where the effect may be coupled to a change in intracellular metabolism. These observations raise the possibility that extracellular ATP (ATP_o) might alter the Ca current of excitable membranes. The Ca current is of major interest because it acts as the trigger for many cellular functions such as secretion, contraction, motility and luminescence. To test our idea, we examined the effects of ATP_o on a well studied Ca current, that of neuronal membranes. As we report here, ATP_o in nanomolar to micromolar concentrations produced substantial increases of I_Ca, and the non-hydrolysable congener of ATP, adenylylimidodiphosphate (AMP-PNP) had an even greater effect. By contrast, intracellular perfusion of ATP in nanomolar quantities had no effects on I_Ca, but with 10⁻⁵–10⁻³ MATP small increases were observed. Intracellular perfusion with AMP-PNP at these doses had no effect on I_Ca. We conclude that ATP_o enhances membrane Ca channel activity by an as yet undetermined mechanism.