TY - JOUR
T1 - ATP-sensitive K+ channel knockout compromises the metabolic benefit of exercise training, resulting in cardiac deficits
AU - Kane, Garvan C.
AU - Behfar, Atta
AU - Yamada, Satsuki
AU - Perez-Terzic, Carmen
AU - O'Cochlain, Fearghas
AU - Reyes, Santiago
AU - Dzeja, Petras P.
AU - Miki, Takashi
AU - Seino, Susumu
AU - Terzic, Andre
PY - 2004/12
Y1 - 2004/12
N2 - 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 (KATP 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 KATP 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 KATP channel activity is required for attainment of the physiologic benefits of exercise training without injury.
AB - 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 (KATP 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 KATP 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 KATP channel activity is required for attainment of the physiologic benefits of exercise training without injury.
UR - http://www.scopus.com/inward/record.url?scp=5744239278&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=5744239278&partnerID=8YFLogxK
U2 - 10.2337/diabetes.53.suppl_3.S169
DO - 10.2337/diabetes.53.suppl_3.S169
M3 - Article
C2 - 15561907
AN - SCOPUS:5744239278
SN - 0012-1797
VL - 53
SP - S169-S175
JO - Diabetes
JF - Diabetes
IS - SUPPL. 3
ER -