Cardiac atp-sensitive k+ channels: regulation by intracellular
nucleotides and potassium channel opening drugs.
Terzic, Andr[acute]e, Arshad Jahangir, and Yoshihisa Kurachi.
Division of Cardiovascular Diseases, Department of Internal
Medicine, and Department of Pharmacology, Mayo Clinic, Mayo
Foundation, Rochester, MN 55905, USA, and Department of Pharmacology
II, Faculty of Medicine, Osaka University, Suita, Osaka 565,
Japan
APStracts 2:0081C, 1995.
ATP- sensitive K+ (KATP) channels are present at high density in
membranes of cardiac cells where they regulate cardiac function
during cellular metabolic impairment. KATP channels have been
implicated in the shortening of the action potential duration and the
cellular loss of K+ that occurs during metabolic inhibition. KATP
channels have been associated with the cardioprotective mechanism of
ischemia-related preconditioning. Intracellular ATP (ATPi) is the
main regulator of KATP channels. ATPi has two functions: (a) to close
the channel (ligand function), and (b) in the presence of Mg2+, to
maintain the activity of KATP channels (presumably through an
enzymatic reaction). KATP channel activity is modulated by
intracellular nucleoside diphosphates which antagonize the ATPi
-induced inhibition of channel opening or induce KATP channels to
open. How nucleotides will affect KATP channels depends on the state
of the channel. Potassium channel opening drugs are pharmacological
agents which enhance KATP channel activity through different
mechanisms, and have great potential in the management of
cardiovascular conditions. KATP channel activity is also modulated by
neurohormones. Adenosine, through the activation of a GTP- binding
protein, antagonizes the ATPi-induced channel closure. Understanding
the molecular mechanisms that underlie KATP channel regulation should
prove essential to further define the function of KATP channels and
to elucidate the pharmacological regulation of this channel protein.
Since the molecular structure of the KATP channel has now become
available, it is anticipated that major progress in the KATP channel
field will be achieved.
Received 3 January 1995; accepted in final form 5 January 1995.
APS Manuscript Number C49-5.
Article publication pending Am. J. Physiol. (Cell Physiology).
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 28 February 1995.