From the Department of Pharmacology and Toxicology, Medical College of
Wisconsin, Milwaukee.
Correspondence to Garrett J. Gross, PhD, Department of Pharmacology and Toxicology, Medical College of Wisconsin, 8701 Watertown Plank Rd, Milwaukee, WI 53226. E-mail ggross@mcw.edu
The ATP-dependent potassium
channels (KATP channels) were originally
identified in isolated membrane patches prepared from guinea pig
ventricular myocytes by Noma1 in
1983. Since their discovery in cardiac cells,
KATP channels have also been discovered in many
other tissues, such as smooth muscle, skeletal muscle, pancreas, and
brain, in which they have been shown to couple cellular
metabolism to membrane electrical
activity.2 Primarily on the basis of studies
using pharmacological tools, openers of KATP
channels have been shown to elicit cardioprotective effects, whereas
KATP channel antagonists have been
shown to block the cardioprotective effects of
KATP channel openers and the powerful protective
effect produced by single or multiple brief episodes of
ischemia to reduce myocardial infarct size, a phenomenon called
ischemic preconditioning.3 Because the
results of these previous studies were obtained indirectly by the use
of pharmacological agonists and antagonists, the results of
the present study published by Jovanovic and
colleagues4 in this issue of
Circulation are particularly exciting and are relevant for
helping to clearly define an important role for the
endogenous KATP channel protein
subunits in conferring the cardioprotective effects of
KATP channel openers and ischemic
preconditioning. In this elegant study by Jovanovic and coworkers, the
authors transfected KATP-deficient COS-7 cells
with the Kir 6.2/SUR 2A genes, which Okuyama et
al5 recently showed to form functional
KATP channels in HEK 293T cells and to possess
the main properties of native KATP channels in
terms of activation by pinacidil and nicorandil but not diazoxide,
channel rundown, and regulation
© 1998 American Heart Association, Inc.
Editorials
Recombinant Cardiac ATP-Sensitive Potassium Channels and Cardioprotection
Key Words: Editorials • potassium • calcium • hypoxia • ischemia • molecular biology