title: The effects of the inotropic agent EMD 57033 on activation and relaxation kinetics in frog skinned skeletal muscle.
abstract: 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.
authors: University Laboratory of Physiology, Parks Road, Oxford OX1 3PT, UK.
authors: S
authors: S
authors: Lipscomb-Allhouse
authors: I P
authors: IP
authors: Mulligan
authors: C C
authors: CC
authors: Ashley
mesh_terms: D000818:Animals; D002316:Cardiotonic Agents / Q000494:pharmacology*; D002614:Chelating Agents / Q000494:pharmacology; D003979:Diazonium Compounds; D004533:Egtazic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D006652:Histological Techniques; D066298:In Vitro Techniques; D007700:Kinetics; D018482:Muscle, Skeletal / Q000187:drug effects* / Q000502:physiology*; D010642:Phenoxyacetates; D011804:Quinolines / Q000494:pharmacology*; D011896:Rana temporaria; D013829:Thiadiazines / Q000494:pharmacology*
chemical_list: D002316:Cardiotonic Agents; D002614:Chelating Agents; D003979:Diazonium Compounds; D010642:Phenoxyacetates; D011804:Quinolines; D013829:Thiadiazines; C070609:EMD 53998; C063685:diazo-2; C085112:2-nitrophenyl-EGTA; D004533:Egtazic Acid