doi: 10.1161/CIRCRESAHA.108.189738
© 2008 American Heart Association, Inc.
Editorials |
Sulfonylurea Receptor Expression Heterogeneity Suggests Chamber-Specific Roles for Sarcolemmal KATP Channels in Heart
From the Departments of Physiology and Medicine, Division of Cardiology, University Health Network, University of Toronto, Ontario, Canada.
Correspondence to Dr Peter H. Backx, DVM, PhD, 150 College St, Fitzgerald Building, Room 68, Toronto, Ontario, M5S 3E2, Canada. E-mail p.backx@utoronto.ca
See related articles, pages 1458–1465
Key Words: electrophysiology • metabolism • KATP channels • arrhythmias • preconditioning • atrium • ventricle
An extract of the first 250 words of the full text is provided, because this article has no abstract. |
The discovery of ATP-sensitive K+ currents (KATP) offered an ideal molecular mechanism for coupling energy availability to excitability, function, and ATP consumption in myocardium,1 as well as other excitable tissues such as pancreatic β cells,2 wherein these channels regulate excitation–secretion coupling and are targets for antidiabetic drugs like sulfonylureas.3 With the cloning of the genes underlying KATP channels, it became clear that these channels were comprised of heteromultimers of 4 inwardly rectifying K+ channels (Kir6.1 or Kir6.2) and 4 ATP-binding cassette sulfonylurea receptors (SUR1 or SUR2).4 Importantly, KATP channels with different molecular constituents show distinct functional and regulatory properties that correlate with the response of KATP channels in various excitable cells, presumably to meet the diverse, and often unique, energy-sensing requirements between different tissues. For example, KATP channels are formed almost exclusively by Kir6.2 and SUR1 genes in pancreatic β cells,4 where these channels use the relative MgADP/MgATP ratio to tightly couple subplasmamembrane glucose levels with insulin release by modulating membrane potential and thereby calcium influx.5 By contrast, sarcolemmal KATP channels in cardiomyocytes (as well as skeletal muscle) have been shown to be comprised primarily of coassembled Kir6.2 and SUR2A proteins.6 Although the role of cardiac sarcolemmal KATP channels in cardiomyocytes is incompletely understood, cardiac sarcolemmal KATP channels appear to coordinate energy consumption with energy availability during periods of stress induced by ischemia, changes in workload, or adrenergic stimulation by modulating the action potential profile.7–9 In addition, sarcolemmal KATP channels also participate in the phenomenon of ischemic preconditioning,10,11 although
Related Article:
Circ. Res. 2008 103: 1458-1465.