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, as well as other excitable tissues such as pancreatic β cells, wherein these channels regulate excitation–secretion coupling and are targets for antidiabetic drugs like sulfonylureas. 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. 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. 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. In addition, sarcolemmal KATP channels also participate in the phenomenon of ischemic preconditioning, although putative KATP channels in the mitochondrial appear to play the dominant role. Regardless, the diversity of KATP channel function in cardiomyocytes, combined with an observed lack of correlation between KATP channel activity and global ATP/ADP ratios in myocardium, suggested that other factors were involved in the regulation of KATP in these cells. For instance, KATP channels are constituents of macromolecular complexes containing various signaling and metabolic enzymes that are assembled into local metabolic subdomains of the cell and are postulated to monitor the energy status by measuring changes in energy flux. Another obvious potential source of diversity in KATP signaling could arise if other KATP proteins are also constituents of cardiac sarcolemmal KATP channels. Indeed, in this issue of Circulation Research, Flagg et al17 use mice lacking the SUR1 gene (SUR1−/−) to clearly establish, using an impressive combination of biochemical and electrophysical measurements along with careful analyses, that sarcolemmal KATP channels in the atrial cardiomyocytes consist of Kir6.2 and SUR1 proteins. Furthermore, although the pharmacological results are consistent with the conclusion that ventricular KATP channels are primarily comprised of Kir6.2 and SUR2A, it appears that low levels of SUR1 may be functionally expressed in ventricular myocytes.