ATP-sensitive K+ channel knockout compromises the metabolic benefit of exercise training, resulting in cardiac deficits.
Exercise training elicits a metabolic and cardiovascular response that underlies fitness. The molecular mechanisms that orchestrate this adaptive response and secure the wide-ranging gains of a regimented exercise program are poorly understood. Formed through association of the Kir6.2 pore and the sulfonylurea receptor, the stress-responsive ATP-sensitive K(+) channels (K(ATP) channels), with their metabolic-sensing capability and broad tissue expression, are potential candidates for integrating the systemic adaptive response to repetitive exercise. Here, the responses of mice lacking functional Kir6.2-containing K(ATP) channels (Kir6.2-KO) were compared with wild-type controls following a 28-day endurance swimming protocol. While chronic aquatic training resulted in lighter, leaner, and fitter wild-type animals, the Kir6.2-KO manifested less augmentation in exercise capacity and lacked metabolic improvement in body fat composition and glycemic handling with myocellular defects. Moreover, the repetitive stress of swimming unmasked a survival disadvantage in the Kir6.2-KO, associated with pathologic calcium-dependent structural damage in the heart and impaired cardiac performance. Thus, Kir6.2-containing K(ATP) channel activity is required for attainment of the physiologic benefits of exercise training without injury.
Kane
Garvan C
GC
Division of Cardiovascular Diseases, Department of Medicine, Mayo Clinic College of Medicine, Rochester, MN 55905, USA.
Behfar
Atta
A
Yamada
Satsuki
S
Perez-Terzic
Carmen
C
O'Cochlain
Fearghas
F
Reyes
Santiago
S
Dzeja
Petras P
PP
Miki
Takashi
T
Seino
Susumu
S
Terzic
Andre
A
D000818:Animals; D005947:Glucose / Q000378:metabolism; D006321:Heart / Q000503:physiopathology*; D006331:Heart Diseases / Q000235:genetics*; D051379:Mice; D018345:Mice, Knockout; D010805:Physical Conditioning, Animal / Q000502:physiology*; D024661:Potassium Channels, Inwardly Rectifying / Q000172:deficiency* / Q000235:genetics / Q000502:physiology*; D013550:Swimming; D000099161:Kcnj11 Channel
D005947:Glucose; D024661:Potassium Channels, Inwardly Rectifying; D000099161:Kcnj11 Channel