MECHANISM OF ACTION OF ENDOTHELIN IN RAT CARDIAC-MUSCLE - CROSS-BRIDGE KINETICS AND MYOSIN LIGHT-CHAIN PHOSPHORYLATION

1. The molecular mechanism of inotropic action of endothelin was inves tigated in rat ventricular muscle by studying its effects on character istics of isometric twitch, barium-induced steady contracture and the level of incorporation of P-32(i) into myosin light chain 2. 2. Exposu re of rat papillary muscle to endothelin caused an increase in isometr ic twitch force but did not alter the twitch-time parameters. 3. Endot helin did not significantly change the maximum contracture tension but did cause an increase in contracture tension at submaximal levels of activation, without changes in the tension-to-stiffness ratio and kine tics of attached cross-bridges. Kinetics of attached crossbridges were deduced during steady contracture from complex-stiffness values, and in particular from the frequency at which muscle stiffness assumes a m inimum value, f(min). Endothelin did not alter f(min). 4. Endothelin c aused an increase in the level of incorporation of P-32(i) into myosin light chain 2 without a concurrent change in the level of incorporati on of P-32(i) into troyonin I. 5. We conclude that the inotropic actio n of endothelin is not due to an increase in the kinetics of attached cross-bridges, nor due to a change in the force per unit cross-bridge, but may result from an increased divalent cation sensitivity caused b y elevated myosin light chain 2 phosphorylation, resembling post-tetan ic potentiation in fast skeletal muscle fibres.