TAURINE DEPLETION AND EXCITATION-CONTRACTION COUPLING IN RAT MYOCARDIUM

Although the sulfur-containing amino acid taurine is found in high concentrations in mammalian myocardium, its involvement in function of the cardiac myocyte remains unclear. To examine the effects of taurine depletion on cardiac mechanical function, rats were treated in vivo with the taurine transport antagonist guanidinoethane sulfonate (GES). After 6 weeks of treatment, myocardial taurine concentrations were decreased to <40% of control, with no change in tissue DNA content. Right ventricular trabeculas from taurine-depleted rats exhibited significant reductions (P<.05) in isometric twitch force (Ft) at all [Ca2+](0) levels and systolic sarcomere lengths examined. Taurine-depleted trabeculas also exhibited increased passive compliance. A slight (P<.05) rightward shift in the Ft-[Ca2+](0) relation suggested a decrease in the sensitivity of the taurine-depleted muscles to [Ca2+](0). No changes were observed in the force-interval relation, suggesting that the transsarcolemmal Ca2+-handling mechanisms remained unchanged. The fraction of Ca2+ recirculated through the sarcoplasmic reticulum, inferred from the decay of postextrasystolic potentiation, was also not different in the taurine-depleted muscles. When force was expressed relative to the rate of stimulation, length of rest periods, or postextrasystolic potentiation, virtually all curves were superimposable for control and taurine-depleted muscles, suggesting that the deficit was not dependent on Ca2+ handling. Thus, we conclude that in taurine-depleted muscles the force-generating processes showed the same regulation as in control muscle. Furthermore, the substantial deficit in force development is consistent with a reduced population of force generators on the basis of three pieces of evidence. First, when Sr2+ was added to the perfusate to directly activate the contractile proteins, the substantial force deficit of taurine-depleted muscles persisted, indicating that the number of contractile elements was substantially smaller than in control muscles. Second, biochemical analysis revealed a significant reduction in the content of both actin and myosin. Third, the force induced by passive stretch was significantly smaller in taurine-depleted muscles, suggesting a loss of elastic elements. Our results offer new information regarding the etiology of cardiomyopathy induced by taurine deficiency.