Recombinant Cardiac ATP-Sensitive K + Channel Subunits Confer Resistance To Chemical Hypoxia-Reoxygenation Injury
- 13 October 1998
- journal article
- other
- Published by Wolters Kluwer Health in Circulation
- Vol. 98 (15), 1548-1555
- https://doi.org/10.1161/01.cir.98.15.1548
Abstract
Background —Opening of cardiac ATP-sensitive K + (K ATP ) channels has emerged as a promising but still controversial cardioprotective mechanism. Defining K ATP 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 —K ATP channel–deficient COS-7 cells were found to be vulnerable to chemical hypoxia-reoxygenation injury that induced significant cytosolic Ca 2+ loading (from 97±3 to 236±11 nmol/L). In these cells, the potassium channel opener pinacidil (10 μmol/L) did not prevent Ca 2+ 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 K ATP 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 (Ca 2+ concentration from 99±7 to 127±11 nmol/L; P >0.05). Both properties were abolished by the K ATP 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 K ATP channels, pinacidil did not protect against hypoxia-reoxygenation. Conclusions —The fact that transfer of cardiac K ATP channel subunits protected natively K ATP channel–deficient cells provides direct evidence that the cardiac K ATP channel protein complex harbors intrinsic cytoprotective properties. These findings validate the concept that targeting cardiac K ATP channels should be considered a valuable approach to protect the myocardium against injury.Keywords
This publication has 36 references indexed in Scilit:
- Ischemic preconditioningCurrent Opinion in Cardiology, 1997
- Pharmacology of ATP-sensitive potassium channel (KATP) openers in models of myocardial ischemia and reperfusionCanadian Journal of Physiology and Pharmacology, 1997
- Adenosine Prevents Hyperkalemia-Induced Calcium Loading in Cardiac Cells: Relevance for CardioplegiaThe Annals of Thoracic Surgery, 1997
- A Family of Sulfonylurea Receptors Determines the Pharmacological Properties of ATP-Sensitive K+ ChannelsNeuron, 1996
- Preconditioning the human myocardium: Recent advances and aspirations for the development of a new means of cardioprotection in clinical practiceCardiovascular Drugs and Therapy, 1995
- Reconstitution of I KATP : An Inward Rectifier Subunit Plus the Sulfonylurea ReceptorScience, 1995
- Glyburide-reversible cardioprotective effect of BMS-180448 is independent of action potential shorteningCardiovascular Research, 1995
- Activation of ATP-sensitive potassium channels: a novel pharmacological approach to myocardial protection?Cardiovascular Research, 1995
- Activation of ATP-sensitive potassium channels: a novel pharmacological approach to myocardial protection?Cardiovascular Research, 1995
- Dualistic behavior of ATP-sensitive K+ channels toward intracellular nucleoside diphosphatesNeuron, 1994