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 (IK(ATP)), appearing during dialysis of rat isolated ventricular myocytes with a low-ATP (100 microM) internal solution under whole-cell patch-clamp conditions, were examined in the presence of a P1 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 IK(ATP) once IK(ATP) had already been partially activated during the low-ATP dialysis. 3. Analogues of ATP, alpha, beta-methyleneadenosine 5'-triphosphate (alpha, beta meATP), 2-methylthioadenosine triphosphate (2MeSATP), adenosine 5'-O-3-thiotriphosphate (ATP gamma S) similarly facilitated IK(ATP). UTP and ADP were very weak agonists while AMP and adenosine had no detectable effect. 4. The half-maximal stimulating concentration (C50) of alpha, beta meATP, an analogue that did not elicite the interfering inward cationic current was 1.5 microM. Similar apparent C50 (1-2 microM) were observed for ATP and analogues tested with somewhat less maximal effect of ATP gamma S. 5. Suramin, a nonselective P2-purinoceptor antagonist, altered IK(ATP) at the relatively high concentration required to inhibit purinoceptors. Pyridoxal-phosphate-6-azophenyl-2',4'-disulphonic acid (PPADS), a supposedly predominantly P2x-purinoceptor antagonist, at micromolar concentration inhibited the transient inward current but did not block the facilitation of IK(ATP). 6. Our results demonstrate that ATP and its analogues facilitate IK(ATP) in rat ventricular myocytes by stimulation of non-P1-, non-P2x-purinoceptors.
Babenko
A P
AP
INSERM U.390, CHU Arnaud de Villeneuve, Montpellier, France.
Vassort
G
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D000255:Adenosine Triphosphate / Q000031:analogs & derivatives / Q000494:pharmacology*; D000818:Animals; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D006352:Heart Ventricles / Q000187:drug effects / Q000378:metabolism; D008297:Male; D009206:Myocardium / Q000378:metabolism*; D018408:Patch-Clamp Techniques; D015221:Potassium Channels / Q000819:agonists*; D011732:Pyridoxal Phosphate / Q000031:analogs & derivatives; D051381:Rats; D017208:Rats, Wistar; D011983:Receptors, Purinergic / Q000187:drug effects / Q000502:physiology*; D013498:Suramin
D015221:Potassium Channels; D011983:Receptors, Purinergic; C077792:pyridoxal phosphate-6-azophenyl-2',4'-disulfonic acid; D011732:Pyridoxal Phosphate; D013498:Suramin; D000255:Adenosine Triphosphate