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 fro g skinned skeletal muscle fibres at 12 degreesC to provide a baseline for s keletal muscle studies and for comparison with cardiac fibres. The activati on and relaxation of fibres were induced by laser flash photolysis of the c aged calcium NP-EGTA, and caged calcium chelator diazo-2 respectively. EMD 57033 (10 muM) slightly increased the rate of relaxation (rate constant k(1 ) 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 (k(1)=9.6 +/-0.9 s(-1) in c ontrol conditions, 9.7 +/-1.6 s(-1) with EMD 57033). The effect of the opti cal isomer of EMD 57033, EMD 57439, was examined on steady-state force and relaxation rate. EMD57439 (10 muM) slowed the rate of relaxation (k(1)=20.5 +/-2.4 s(-1)) but had no effect on the maximal calcium-activated force whe reas 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 forc e per cross-bridge is discussed.