ATP-sensitive K+ currents in cerebral arterial smooth muscle: pharmacological and hormonal modulation.
Calcitonin gene-related peptide (CGRP), hypoxia, and synthetic activators of ATP-sensitive potassium (KATP) channels (e.g., pinacidil and levcromakalim) cause dilation of cerebral arteries that are attenuated by the KATP channel inhibitor glibenclamide. We have identified and characterized KATP currents in smooth muscle cells isolated from rabbit cerebral arteries, using the whole cell configuration of the patch-clamp technique. Pinacidil (10 microM) and levcromakalim (10 microM) increased glibenclamide-sensitive currents about sixfold in cells dialyzed with 0.1 mM ATP. Glibenclamide-sensitive currents in the presence of pinacidil were potassium selective, voltage independent, and reduced about threefold by elevating intracellular ATP from 0.1 to 3.0 mM. External tetraethylammonium and 4-aminopyridine at millimolar concentrations reduced pinacidil-induced currents, whereas iberiotoxin, a blocker of calcium-activated potassium channels, had no effect. The vasoconstrictors serotonin and histamine also inhibited pinacidil-induced currents. The vasodilators CGRP and adenosine, in contrast, increased glibenclamide-sensitive potassium currents. We conclude that cerebral artery smooth muscle cells have KATP channels that are regulated by endogenous vasoconstrictors and vasodilators. We propose that these channels are involved in the dilation of cerebral arteries to CGRP and synthetic vasodilators.
Kleppisch
T
T
Department of Pharmacology, University of Vermont, Colchester 05446, USA.
Nelson
M T
MT
D015761:4-Aminopyridine / Q000494:pharmacology; D000255:Adenosine Triphosphate / Q000502:physiology*; D000818:Animals; D002536:Cerebral Arteries / Q000378:metabolism*; D004553:Electric Conductivity; D005905:Glyburide / Q000494:pharmacology; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000378:metabolism*; D026902:Potassium Channel Blockers; D015221:Potassium Channels / Q000187:drug effects / Q000502:physiology*; D011817:Rabbits; D019789:Tetraethylammonium; D013757:Tetraethylammonium Compounds / Q000494:pharmacology; D014662:Vasoconstrictor Agents / Q000494:pharmacology; D014665:Vasodilator Agents / Q000494:pharmacology
D026902:Potassium Channel Blockers; D015221:Potassium Channels; D013757:Tetraethylammonium Compounds; D014662:Vasoconstrictor Agents; D014665:Vasodilator Agents; D019789:Tetraethylammonium; D000255:Adenosine Triphosphate; D015761:4-Aminopyridine; D005905:Glyburide