Paradoxical Effects of Epinephrine on Excitation-Contraction Coupling in Cardiac Muscle

Abstract

The possibility that the inotropic action of epinephrine might be mediated through an effect on the excitation-contraction coupling process was explored, using techniques for measurement of isometric tension, together, in some experiments, with recording of the transmembrane potential time course from short lengths of cat papillary muscle. Four observations relevant to this question, have been made: (1) Extracellular calcium concentration can be raised and extracellular sodium concentration lowered to a point at which contraction cannot be further augmented by the addition of epinephrine. (2) The early relaxation induced by epinephrine occurs well in advance of membrane repolarization. This effect is antagonized by increasing calcium concentration, although the action of epinephrine in augmenting developed tension appears to be synergistic with that of calciumion. (3) The length-tension relationship is undiminished in the calcium-rich (8.1 mmoles /liter), sodium-poor (75 mEq/liter) medium. (4) Epinephrine, in a dose (1 to 2 µg/ml) which markedly augments twitch tension, profoundly decreases tension developed by the same preparation during a potassium chloride contracture; this is the case for both the frog ventricle strip and the cat papillary muscle. A preliminary concept of the ionic mechanism of excitation-contraction coupling, compatible with these facts and with some others, is described.