ALTERED FORCE KINETICS IN NORMAL AND STRESSED HEARTS

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Different isoenzymes of ventricular myosin have been reported in the mammalian heart. In some species (rat, rabbit) differences in myocardial performance have been correlated with differences in ventricular isomyosin pattern. Several investigators have suggested the possibility that myocardial performance and isomyosin pattern are correlated because crossbridge cycling characteristics are different in muscles with different isomyosins. The objective of the proposed research is to investigate the isomyosin dependence of crossbridge cycling characteristics. Trabeculae, taken from rats treated so that their hearts have mostly either the V1 or the V3 isoform of myosin, will be chemically skinned (to allow precise experimental control of the ionic environment of the myofibrils) and activated in an isometric contraction. At the plateau of isometric force small amplitude rapid length changes will be applied and the resulting force transients will be recorded. The muscles will be saved for subsequent determination of their isomyosin patterns by gel electrophoresis. We will test whether the force transients reflect crossbridge cycling characteristics by investigating the effects of temperature and substrate (MgATP) concentration on the characteristics of the transients. Information about crossbridge cycling characteristics in muscles with different extremes of myosin isoenzyme pattern will be derived from the amplitudes and time courses of the several phases of the force transient response; this information will be extracted by fitting sums of exponentials to the force transients. The results of this research will provide information concerning the influence of myosin isoenzyme type on the kinetics of the fundamental force generating interaction of myosin with actin. In addition, these results may be helpful in explaining the performance changes observed in stress-adapted myocardium with altered myosin isoenzyme patterns.