AJP - Cell Physiology, Vol 262, Issue 5 C1220-C1227, Copyright © 1992 by American Physiological Society
ATP-sensitive potassium channel is essential to maintain basal coronary vascular tone in vivo
F. F. Samaha, F. W. Heineman, C. Ince, J. Fleming and R. S. Balaban
Laboratory of Cardiac Energetics, National Heart, Lung, and Blood Institute, Bethesda, Maryland 20892.
Glibenclamide, a known selective inhibitor of ATP-sensitive potassium
channels, was infused into the coronary vasculature of anesthetized dogs
and of isolated perfused rabbit hearts to assess the role of this channel
in the maintenance of basal coronary resistance. Infusion of glibenclamide
at a concentration of 55-80 microM in the dogs resulted in a twofold
steady-state increase in coronary resistance with resultant tissue
ischemia. Infusion of 1 microM glibenclamide in the isolated hearts
resulted in a 67% increase in coronary resistance with resultant tissue
ischemia. The ischemic changes were reversible upon removal of the drug.
These findings indicate that the ATP-sensitive K+ channel plays a
significant role in the maintenance of basal coronary resistance in vivo.
Higher concentrations of glibenclamide (80-100 microM) in the in vivo dog
heart consistently gave rise to an oscillating pattern of coronary flow.
These oscillations were either eliminated or decreased in amplitude and
frequency by the infusion of 8-phenyltheophylline, a specific competitive
inhibitor of adenosine receptors. 31P-nuclear magnetic resonance
spectroscopy performed at the peaks and troughs of these oscillations
revealed oscillation of the phosphorylation potential at the same
frequency. Thus adenosine release caused by tissue ischemia appears to play
a major role in creating the oscillating pattern of coronary blood flow,
that occurs during the inhibition of ATP-sensitive K+ channels by
glibenclamide.
