Muscle KATP Channels: Recent Insights to Energy Sensing and Myoprotection

Flagg TP, Enkvetchakul D, Koster JC, Nichols CG. Muscle K-ATP Channels: Recent Insights to Energy Sensing and Myoprotection. Physiol Rev 90: 799-829, 2010; doi:10.1152/physrev.00027.2009.-ATP-sensitive potassium (K-ATP) channels are present in the surface and internal membranes of cardiac, skeletal, and smooth muscle cells and provide a unique feedback between muscle cell metabolism and electrical activity. In so doing, they can play an important role in the control of contractility, particularly when cellular energetics are compromised, protecting the tissue against calcium overload and fiber damage, but the cost of this protection may be enhanced arrhythmic activity. Generated as complexes of Kir6.1 or Kir6.2 pore-forming subunits with regulatory sulfonylurea receptor subunits, SUR1 or SUR2, the differential assembly of K-ATP channels in different tissues gives rise to tissue-specific physiological and pharmacological regulation, and hence to the tissue-specific pharmacological control of contractility. The last 10 years have provided insights into the regulation and role of muscle K-ATP channels, in large part driven by studies of mice in which the protein determinants of channel activity have been deleted or modified. As yet, few human diseases have been correlated with altered muscle K-ATP activity, but genetically modified animals give important insights to likely pathological roles of aberrant channel activity in different muscle types.