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 microM) 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 microM carbachol or 10 microM adenosine, ATP (1-100 microM) 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 microM) or reactive blue-2 (30 microM), but not by theophylline (500 microM), indicating the involvement of P2 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 microM carbachol in the cell-attached mode. Thus, P2 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.
Hara
Y
Y
Department of Pharmacology, School of Medicine, Chiba University, Japan. hara@vmas.kitasato-u.ac.jp
Nakaya
H
H
D000255:Adenosine Triphosphate / Q000494:pharmacology*; D000818:Animals; D002217:Carbachol / Q000494:pharmacology; D006168:Guinea Pigs; D006321:Heart / Q000187:drug effects*; D008564:Membrane Potentials / Q000187:drug effects*; D011188:Potassium / Q000494:pharmacology; D011976:Receptors, Muscarinic / Q000187:drug effects* / Q000378:metabolism
D011976:Receptors, Muscarinic; D000255:Adenosine Triphosphate; D002217:Carbachol; D011188:Potassium