Intracellular ADP activates ATP-sensitive K+ channels in vascular smooth muscle cells of the guinea pig portal vein.
Vasodilatation following tissue ischemia is assumed to partially result from activation of ATP-dependent K+ channels (KATP). To assess the effect of cytosolic adenosine nucleotides, the balance of which depends on tissue pO2, on KATP, we have measured steady state outward currents (SSC) by the whole-cell clamp technique in smooth muscle cells of the guinea pig portal vein at different concentrations of ATP and ADP in the pipette solution. Glibenclamide, a selective inhibitor of KATP, was used as a pharmacological tool. With no nucleotides in the pipette solution (Ca(2+)-free), the SSC determined at +20 mV was unaffected by glibenclamide, while with 0.1 mM ATP or with 0.1 mM ADP, the SSC exhibited a glibenclamide-sensitive component indicating activation of KATP. At 5 mM ATP and no ADP, hardly any effect of glibenclamide on the SSC was detected, suggesting inhibition of KATP by this high concentration of ATP. With 0.1 mM ADP at 5 mM ATP however, activation of KATP was achieved. At 10(-7) M Ca2+ in the pipette solution, an increased SSC was measured, but the responses to the nucleotides and/or glibenclamide were not modified. These findings suggest that in vivo, ADP may be involved in the regulation of vascular KATP, linking tissue pO2 with vascular tone and tissue perfusion.
Pfründer
D
D
II. Physiologisches Institut, Universität Heidelberg, Germany.
Anghelescu
I
I
Kreye
V A
VA
D000244:Adenosine Diphosphate / Q000494:pharmacology*; D000255:Adenosine Triphosphate / Q000494:pharmacology*; D000818:Animals; D004553:Electric Conductivity; D005905:Glyburide / Q000494:pharmacology; D006168:Guinea Pigs; D009131:Muscle, Smooth, Vascular / Q000502:physiology*; D011169:Portal Vein; D015221:Potassium Channels / Q000187:drug effects / Q000502:physiology*; D014664:Vasodilation
D015221:Potassium Channels; D000244:Adenosine Diphosphate; D000255:Adenosine Triphosphate; D005905:Glyburide