Muscle KATP channels: Recent insights to energy sensing and myoprotection

Thomas P. Flagg, Decha Enkvetchakul, Joseph C. Koster, Colin G. Nichols

Research output: Contribution to journalReview articlepeer-review

191 Scopus citations

Abstract

ATP-sensitive potassium (KATP) 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 KATP 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 KATP 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 KATP activity, but genetically modified animals give important insights to likely pathological roles of aberrant channel activity in different muscle types.

Original languageEnglish
Pages (from-to)799-829
Number of pages31
JournalPhysiological reviews
Volume90
Issue number3
DOIs
StatePublished - Jul 2010

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