Circulation research
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Circulation research · Jul 1995
Comparative StudyL-methionine augments mammalian myocardial contraction by sensitizing the myofilament to Ca2+.
L-Methionine is an essential amino acid that has been reported to have a potent positive inotropic effect on the mammalian myocardium. We studied the mechanisms of the inotropic effect in ventricular myocardium from the rabbit. In the isolated coronary-perfused whole heart, L-methionine in a millimolar range exerted concentration-dependent positive inotropic effects on the isovolumic left ventricle, which were associated with negative lusitropic effects (prolonged time course of relaxation). ⋯ The [Ca2+]i-tension relation shifted to the left compared with that obtained in response to [Ca2+]o. In saponin (250 micrograms/mL)-treated skinned preparations, 3 mmol/L L-methionine also shifted the force-pCa curve to the left by 0.16 pCa units. This is the first demonstration that an essential amino acid directly acts on the myofilaments and modulates their responsiveness to Ca2+, thereby producing a positive inotropic effect.