Purinergic facilitation of ATP‐sensitive potassium current in rat ventricular myocytes

1 The effects of different purinergic agonists on the cardiac adenosine 5′‐triphosphate (ATP)‐sensitive potassium current ( I K(atp) ) appearing during dialysis of rat isolated ventricular myocytes with a low‐ATP (100 μm) internal solution under whole‐cell patch‐clamp conditions, were examined in the presence of a P 1 purinoceptor antagonist. 2 The extracellular application of ATP in the micromolar range induced, besides known inward currents through cationic and chloride channels, the facilitation of I K(atp) once I K(atp) had already been partially activated during the low‐ATP dialysis. 3 Analogues of ATP, α,β‐methyleneadenosine 5′‐triphosphate (α,βmeATP), 2‐methylthioadenosine triphosphate (2MeSATP), adenosine 5′‐O‐3‐thiotriphosphate (ATPγS) similarly facilitated I K(atp) . UTP and ADP were very weak agonists while AMP and adenosine had no detectable effect. 4 The half‐maximal stimulating concentration (C 50 ) of α,βmeATP, an analogue that did not elicite the interfering inward cationic current was 1.5 μm. Similar apparent C 50 (1–2 μm) were observed for ATP and analogues tested with somewhat less maximal effect of ATPγS. 5 Suramin, a nonselective P 2 ‐purinoceptor antagonist, altered I K(atp) at the relatively high concentration required to inhibit purinoceptors. Pyridoxal‐phosphate‐6‐azophenyl‐2′,4′‐disulphonic acid (PPADS), a supposedly predominantly P 2X ‐purinoceptor antagonist, at micromolar concentration inhibited the transient inward current but did not block the facilitation of I K(atp) . 6 Our results demonstrate that ATP and its analogues facilitate I K(atp) in rat ventricular myocytes by stimulation of non‐P 1 ‐, non‐P 2X ‐purinoceptors.