Dual effects of extracellular ATP on the muscarinic acetylcholine receptor-operated K + current in guinea-pig atrial cells

Abstract

Adenosine 5′-triphosphate (ATP) is stored in sympathetic and parasympathetic nerve terminals and co-released with norepinephrine and acetylcholine during nerve stimulation. In the heart in situ parasympathetic nerve is tonically stimulated and the activated muscarinic acetylcholine-receptor-operated K + current ( I K.ACh) plays an important role in the repolarization of the atrial action potential, the sinoatrial node automaticity and the atrioventricular conduction. In the present study, effects of extracellular ATP on the I K.ACh activated by carbachol or adenosine were examined in isolated guinea-pig atrial cells by use of the patch-clamp technique. ATP (10 μM) per se produced a transient activation of I K.ACh in atrial cells held at −40 mV. When I K.ACh was preactivated by 1 μM carbachol or 10 μM adenosine, ATP (1–100 μM) produced a transient increase followed by a sustained decrease of the current. These ATP-induced biphasic changes of I K.ACh were abolished by suramin (100 μM) or reactive blue-2 (30 μM), but not by theophylline (500 μM), indicating the involvement of P 2 purinoceptors. ATP also enhanced and then partially reversed the action potential shortening induced by carbachol or adenosine in current-clamped atrial cells. Extracellular ATP did not increase but decreased the openings of the single K ACh channel that were recorded by use of a pipette solution containing 1 μM carbachol in the cell-attached mode. Thus, P 2 purinoceptor stimulation produces dual effects of ATP on the pre-activated I K.ACh and may modulate the chronotropic and inotropic responses during autonomic nerve stimulation. © 1997 Elsevier Science B.V.