Diadenosine tetraphosphate-induced inhibition of ATP-sensitive K+ channels in patches excised from ventricular myocytes.
Diadenosine 5',5''-P1,P4-tetraphosphate (Ap4A) has been termed 'alarmone' due to its role in intracellular signaling during metabolic stress. It is not known whether Ap4A could modulate ATP-sensitive K+ (KATP) channels, a family of channels regulated by the metabolic status of a cell. We applied the single-channel patch-clamp technique to measure the effect of Ap4A on KATP channels. When applied to the intracellular side of patches, excised from guinea-pig ventricular myocytes, Ap4A inhibited KATP channel activity, in a reversible and concentration-dependent (half-maximal concentration approximately 17 microM) manner. We conclude that Ap4A, a naturally occurring diadenosine polyphosphate, is actually an inhibitor of the myocardial KATP channel.
Jovanovic
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Department of Medicine, Mayo Clinic, Mayo Foundation, Rochester, MN 55905, USA.
Terzic
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D000255:Adenosine Triphosphate / Q000502:physiology*; D000818:Animals; D015226:Dinucleoside Phosphates / Q000494:pharmacology*; D006168:Guinea Pigs; D006352:Heart Ventricles / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D066298:In Vitro Techniques; D009206:Myocardium / Q000166:cytology / Q000378:metabolism*; D018408:Patch-Clamp Techniques; D015221:Potassium Channels / Q000187:drug effects / Q000378:metabolism*
D015226:Dinucleoside Phosphates; D015221:Potassium Channels; C020733:diadenosine tetraphosphate; D000255:Adenosine Triphosphate