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Am J Physiol Heart Circ Physiol 276: H1511-H1519, 1999;
0363-6135/99 $5.00
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Vol. 276, Issue 5, H1511-H1519, May 1999

Aging-dependent depression in the kinetics of force development in rat skinned myocardium

Daniel P. Fitzsimons, Jitandrakumar R. Patel, and Richard L. Moss

Department of Physiology, University of Wisconsin School of Medicine, Madison, Wisconsin 53706

Normal aging of the rodent heart results in prominent prolongation of the twitch. We tested the hypothesis that increased expression of beta -myosin heavy chain (MHC), as occurs in the normal aging process in the rodent heart, contributes to the prolongation of the twitch by depressing the kinetics of cross-bridge interaction. Using 3-, 9-, 21-, and 33-mo-old male Fischer 344 × Brown Norway F1 hybrid rats, we examined both the rate of tension development (kCa) and unloaded shortening velocity in chemically skinned myocardium. Although kCa in all four age groups was dependent on the level of Ca2+ activation, both submaximal and maximal kCa were significantly slower in 9-, 21-, and 33-mo-old rats relative to 3-mo-old rats. Furthermore, unloaded shortening velocity was significantly reduced in 9-, 21-, and 33-mo-old rats compared with 3-mo-old rats. Collectively, these data strongly suggest that the aging-related increase in beta -MHC expression results in a progressive slowing of cross-bridge interaction kinetics in skinned myocardium, which most likely contributes to the overall aging-dependent reduction in myocardial functional capacity.

myosin heavy chain; caged calcium; cross-bridge kinetics; Fischer 344 × Brown Norway rats


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