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 (K-ATP) channels (e.g., pinacidil and levcromakalim) cause dilation of cerebral arteries that are attenuated by the K-ATP channel inhibitor glibenclamide. We have identified and characterized K-ATP currents in smooth muscle cells isolated from rabbit cerebral arteries, using the whole cell configuration of the patch-clamp technique. Pinacidil (10 mu M) and levcromakalim (10 mu M) 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 K-ATP 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.