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.
Animals Cardiotonic Agents