A potassium current activated by lemakalim and metabolic inhibition in rabbit mesenteric artery.
K+ channels which are inhibited by intracellular ATP (ATPi) (KATP channels) are thought to be the physiological target site of the K+ channel opening drugs (2) and to underlie a variety of physiological phenomena including hypoxia induced vasodilation. However, electrophysiological evidence for ATPi-regulated K+ currents in smooth muscle is scarce. We, therefore, investigated the effects of one K+ channel opener, lemakalim, and metabolic inhibition on the membrane conductance of freshly dissociated rabbit mesenteric artery smooth muscle cells, using the perforated-patch whole cell recording technique. The cells were metabolically inhibited with 1 mM iodoacetic acid and 50 microM dinitrophenol. Both lemakalim (0.1-3 microM) and metabolic inhibition activated a time-independent and glyburide sensitive K+ current at physiological membrane potentials. The similarities between the lemakalim and metabolic inhibition activated currents suggest that a single class of channels underlies both currents. These results are the first whole-cell current recordings to demonstrate the activation of a smooth muscle membrane conductance by metabolic inhibition, lending support to the view that hypoxia induced vasodilation arises from the activation of KATP channels.
Silberberg
S D
SD
University of Miami, School of Medicine, Department of Molecular and Cellular Pharmacology, FL 33101.
van Breemen
C
C
D000818:Animals; D001578:Benzopyrans / Q000494:pharmacology*; D019806:Cromakalim; D004140:Dinitrophenols / Q000494:pharmacology; D004594:Electrophysiology; D005905:Glyburide / Q000494:pharmacology; D007461:Iodoacetates / Q000494:pharmacology; D019807:Iodoacetic Acid; D008297:Male; D008638:Mesenteric Arteries / Q000166:cytology / Q000378:metabolism / Q000502:physiology*; D011188:Potassium / Q000502:physiology*; D011758:Pyrroles / Q000494:pharmacology*; D011817:Rabbits
D001578:Benzopyrans; D004140:Dinitrophenols; D007461:Iodoacetates; D011758:Pyrroles; D019806:Cromakalim; D011188:Potassium; D005905:Glyburide; D019807:Iodoacetic Acid