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Rochester, MN, United States

Alekseev A.E.,Marriott Heart Diseases Research Program | Reyes S.,Marriott Heart Diseases Research Program | Yamada S.,Marriott Heart Diseases Research Program | Hodgson-Zingman D.M.,Marriott Heart Diseases Research Program | And 10 more authors.
Cell Metabolism | Year: 2010

Metabolic processes that regulate muscle energy use are major determinants of bodily energy balance. Here, we find that sarcolemmal ATP-sensitive K+ (KATP) channels, which couple membrane excitability with cellular metabolic pathways, set muscle energy expenditure under physiological stimuli. Disruption of KATP channel function provoked, under conditions of unaltered locomotor activity and blood substrate availability, an extra energy cost of cardiac and skeletal muscle performance. Inefficient fuel metabolism in KATP channel-deficient striated muscles reduced glycogen and fat body depots, promoting a lean phenotype. The propensity to lesser body weight imposed by KATP channel deficit persisted under a high-fat diet, yet obesity restriction was achieved at the cost of compromised physical endurance. Thus, sarcolemmal KATP channels govern muscle energy economy, and their downregulation in a tissue-specific manner could present an antiobesity strategy by rendering muscle increasingly thermogenic at rest and less fuel efficient during exercise. © 2010 Elsevier Inc. All rights reserved. Source

Reyes S.,Marriott Heart Diseases Research Program | Park S.,Marriott Heart Diseases Research Program | Terzic A.,Marriott Heart Diseases Research Program | Alekseev A.E.,Marriott Heart Diseases Research Program
Critical Reviews in Biochemistry and Molecular Biology | Year: 2010

Uniquely gated by intracellular adenine nucleotides, sarcolemmal ATP-sensitive K+ (KATP) channels have been typically assigned to protective cellular responses under severe energy insults. More recently, KATP channels have been instituted in the continuous control of muscle energy expenditure under non-stressed, physiological states. These advances raised the question of how KATP channels can process trends in cellular energetics within a milieu where each metabolic system is set to buffer nucleotide pools. Unveiling the mechanistic basis of the KATP channel-driven thermogenic response in muscles thus invites the concepts of intracellular compartmentalization of energy and proteins, along with nucleotide signaling over diffusion barriers. Furthermore, it requires gaining insight into the properties of reversibility of intrinsic ATPase activity associated with KATP channel complexes. Notwithstanding the operational paradigm, the homeostatic role of sarcolemmal KATP channels can be now broadened to a wider range of environmental cues affecting metabolic well-being. In this way, under conditions of energy deficit such as ischemic insult or adrenergic stress, the operation of KATP channel complexes would result in protective energy saving, safeguarding muscle performance and integrity. Under energy surplus, downregulation of KATPchannel function may find potential implications in conditions of energy imbalance linked to obesity, cold intolerance and associated metabolic disorders. © 2010 Informa Healthcare USA, Inc. Source

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