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

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 mu M) 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 mu M carbachol or 10 mu M adenosine, ATP (1-100 mu M) 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 mu M) or reactive blue-2 (30 mu M), but not by theophylline (500 mu M), 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 mu M 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. (C) 1997 Elsevier Science B.V.