Myofibril MgATPase activities and energy metabolism in cardiomyopathic mice with diastolic dysfunction.
To study the genomic physiology of cardiac myofibril proteins in the heart, we have successfully created a cardiac troponin I (cTnI; a myofibril protein) gene knockout mouse model using gene targeting techniques. The phenotype of the cTnI gene knockout mouse is a cardiomyopathy with diastolic dysfunction resulting in sudden death in neonates. In the present studies, energy metabolism was analyzed in myocardial cells from cTnI-null hearts. Myofibril MgATPase activities were determined in myocardial cells from either wild-type or cTnI mutant mouse hearts. Furthermore, the quantity and quality of the mitochondria in wild-type and cTnI mutant animals were counted and analyzed. Our results demonstrate that damaged relaxation and increased Ca(2+)-independent force production in cTnI-null hearts is in part related to the increased myofibril MgATPase activities accompanied by an increase in mitochondria quantity and mitochondrial ATPase activities. These data indicate that cardiomyopathies with diastolic dysfunction are different from cardiomyopathies caused by systolic dysfunction. The former involves the damage of cardiac relaxation due to increased MgATPase activities and increased Ca(2+)-independent force production inside of myofilaments, while the latter involves the damage of systolic contraction due to decreased MgATPase activities and decreased force production.
Jia
Yuanyuan
Y
Department of Biomedical Science, Florida Atlantic University, Boca Raton, FL 33431, USA.
Akerman
Sarah
S
Huang
Xupei
X
D000818:Animals; D017301:Ca(2+) Mg(2+)-ATPase / Q000378:metabolism*; D009202:Cardiomyopathies / Q000201:enzymology / Q000209:etiology / Q000378:metabolism*; D003971:Diastole; D004734:Energy Metabolism; D051379:Mice; D018345:Mice, Knockout; D008928:Mitochondria / Q000201:enzymology / Q000473:pathology; D009126:Muscle Relaxation; D009206:Myocardium / Q000473:pathology; D009210:Myofibrils / Q000201:enzymology*; D010641:Phenotype; D019210:Troponin I / Q000235:genetics / Q000502:physiology*
D019210:Troponin I; D017301:Ca(2+) Mg(2+)-ATPase