Myocyte structure, function, and calcium kinetics in the cardiomyopathic hamster heart.
The hereditary cardiomyopathic strain of the Syrian hamster has been studied extensively as a model of cardiomyopathy and heart failure. However, the primary defect underlying the cascade of events leading to heart failure has not been identified. In the present study, isolated cardiac cells were obtained for study from 8-mo-old cardiomyopathic (Bio 14.6) and age-matched normal hamsters (F1B). We examined the relationships among structure, contractile function, and calcium kinetics in these isolated cardiomyocytes. The cardiomyopathic myocytes were wider and longer than controls, and myopathic cells were less calcium tolerant. The sarcoplasmic reticulum and T-tubule systems from myopathic hearts were more abundant as determined by electron microscopy. The amplitude and velocity of contraction was decreased in cardiomyopathic cells, whereas diastolic relaxation velocity was not different between the two groups. The size of the rapidly exchangeable calcium pool determined by 45Ca2+ uptake was significantly increased in cardiomyopathic myocytes. Time-averaged cytosolic Ca2+ in these cells (472 +/- 60 nM) was significantly higher than control (260 +/- 15 nM) as measured by the fura-2 fluorescence ratio. When extracellular Ca2+ ([Ca2+]o) was increased to greater than 1.2 mM, the resulting increase in intracellular calcium concentration was less than that in normal control cells. The corresponding [Ca2+]o-induced increase in amplitude of cell motion was significantly attenuated in the cardiomyopathic cells compared with normal control myocytes. We conclude that distinct abnormalities of contractile function and calcium homeostasis can be identified in single cells isolated from cardiomyopathic hamster hearts.
Sen
L Y
LY
Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts.
O'Neill
M
M
Marsh
J D
JD
Smith
T W
TW
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D009202:Cardiomyopathies / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology; D002469:Cell Separation; D006224:Cricetinae; D003971:Diastole; D007700:Kinetics; D008647:Mesocricetus; D009200:Myocardial Contraction; D009206:Myocardium / Q000378:metabolism / Q000473:pathology*; D009994:Osmolar Concentration; D012016:Reference Values; D013599:Systole; D013997:Time Factors
D002118:Calcium