From the Division of Cardiovascular Diseases, Department of Internal
Medicine, Mayo Clinic and Mayo Foundation, Rochester, Minn.
Correspondence to Andre Terzic, MD, PhD, Division of Cardiovascular Diseases, Department of Medicine, Guggenheim-7F, Mayo Clinic and Foundation, Rochester, MN 55905. E-mail terzic.andre{at}mayo.edu
Background—Opening of cardiac
ATP-sensitive K+ (KATP) channels has emerged as
a promising but still controversial cardioprotective mechanism.
Defining KATP channel function at the level of recombinant
channel proteins is a necessary step toward further evaluation of the
cardioprotective significance of this ion conductance.
Methods and Results—KATP channel–deficient COS-7
cells were found to be vulnerable to chemical
hypoxia-reoxygenation injury that induced
significant cytosolic Ca2+ loading (from 97±3 to 236±11
nmol/L). In these cells, the potassium channel opener pinacidil
(10 µmol/L) did not prevent Ca2+ loading (from 96±3
nmol/L before to 233±12 nmol/L after reoxygenation) or
evoked membrane current. Cotransfection with
Kir6.2/SUR2A genes, which encode cardiac
KATP channel subunits, resulted in a cellular
phenotype that, in the presence of pinacidil (10
µmol/L), expressed K+ current and gained resistance to
hypoxia-reoxygenation (Ca2+
concentration from 99±7 to 127±11 nmol/L; P>0.05).
Both properties were abolished by the KATP channel blocker
glyburide (1 µmol/L). In COS-7 cells transfected with individual
channel subunits Kir6.2 or SUR2A, which
alone do not form functional cardiac KATP channels,
pinacidil did not protect against
hypoxia-reoxygenation.
Conclusions—The fact that transfer of cardiac KATP
channel subunits protected natively KATP channel–deficient
cells provides direct evidence that the cardiac KATP
channel protein complex harbors intrinsic cytoprotective properties.
These findings validate the concept that targeting cardiac
KATP channels should be considered a valuable approach to
protect the myocardium against injury.
© 1998 American Heart Association, Inc.
Basic Science Reports
Recombinant Cardiac ATP-Sensitive K+ Channel Subunits Confer Resistance To Chemical Hypoxia-Reoxygenation Injury
, MD, PhD, DVM, PhD
Key Words: ischemia • hypoxia • reperfusion • potassium channels • calcium
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