Atp-sensitive k+ currents in smooth muscle from rabbit cerebral
arteries: pharmacological and hormonal modulation.
Kleppisch, Thomas, and Mark T. Nelson.
Department of Pharmacology, Smooth Muscle Ion Channel Group,
Vermont Center for Vascular Research, University of Vermont, 55A
South Park Drive, Colchester, Vermont
APStracts 2:0239H, 1995.
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 inhibitor of KATP channels, 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[mu]M) and
levcromakalim (10[mu]M) increased glibenclamide-sensitive currents
about 6-fold in cells dialyzed with 0.1 mM ATP. Glibenclamide
-sensitive currents in the presence of pinacidil were potassium
-selective, voltage-independent, and were reduced about 3-fold 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
Ca2+-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.
Received 12 January 1995; accepted in final form 12 May 1995.
APS Manuscript Number H28-5.
Article publication pending Am. J. Physiol. (Heart Circ. Physiology).
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 6 July 1995.