ATP4- and ATP.Mg inhibit the ATP-sensitive K+ channel of rat ventricular myocytes.
K+ currents were recorded from ATP-sensitive channels in inside-out membrane patches excised from isolated rat ventricular myocytes. ATP-sensitive K+ channel inhibition could be evoked by ATP in the absence of magnesium where most ATP would be present as the free acid ATP4-. Channel inhibition was enhanced when the same total concentration of ATP was applied in the presence of magnesium, where most ATP would be bound as ATP.Mg. Dose-response relationships for ATP-sensitive K+ channel inhibition evoked by ATP had a Hill coefficient of 2 and Ki of 17 and 30 microM for ATP in the presence and absence of magnesium respectively. This was the obverse of the expected results if ATP4- were to be the sole form of ATP to effect channel closure. ATP-sensitive K+ channel inhibition evoked by ATP gamma S, AMP-PNP and AMP-PCP was also enhanced in the presence of magnesium. It is concluded that the ATP-sensitive K+ channel of rat ventricular myocytes binds and is closed by both the free-acid and divalent-cation-bound forms of ATP.
Findlay
I
I
Laboratoire de Physiologie Comparée (UA CNRS 1121), Université dé Paris XL, Orsay, France.
D000255:Adenosine Triphosphate / Q000494:pharmacology*; D000818:Animals; D004305:Dose-Response Relationship, Drug; D006352:Heart Ventricles / Q000166:cytology; D008274:Magnesium / Q000494:pharmacology*; D010210:Papillary Muscles / Q000166:cytology* / Q000502:physiology; D015221:Potassium Channels / Q000187:drug effects* / Q000502:physiology; D051381:Rats; D016276:Ventricular Function
D015221:Potassium Channels; D000255:Adenosine Triphosphate; D008274:Magnesium