The effects of the inotropic agent EMD 57033 on activation and relaxation kinetics in frog skinned skeletal muscle.

The effect of the cardiotonic sensitizing drug EMD 57033 was studied in frog skinned skeletal muscle fibres at 12 degrees C to provide a baseline for skeletal muscle studies and for comparison with cardiac fibres. The activation and relaxation of fibres were induced by laser flash photolysis of the caged calcium NP-EGTA, and caged calcium chelator diazo-2 respectively. EMD 57033 (10 microM) slightly increased the rate of relaxation (rate constant k1 changing from 24.0 +/- 2.9 s-1 in control to 28.1 +/- 3.2 s-1) but had no significant effect on the rate of activation (k1 = 9.6 +/- 0.9 s-1 in control conditions, 9.7 +/- 1.6 s-1 with EMD 57033). The effect of the optical isomer of EMD 57033, EMD 57439, was examined on steady-state force and relaxation rate. EMD57439 (10 microM) slowed the rate of relaxation (k1 = 20.5 +/- 2.4 s-1) but had no effect on the maximal calcium-activated force whereas EMD 57033 increased it by 16.5 +/- 5.7%. These results are compared to earlier results from this laboratory in guinea-pig skinned trabeculae, and a possible model for the action of EMD 57033 whereby the drug enhances force per cross-bridge is discussed.