The cardiotonic agent (+)-EMD-57033 increases maximal force and myofilament calcium sensitivity in rat ventricular cells, likely by increasing the number of attached cross bridges.
The effects of the Ca sensitizer (+)-EMD-57033 were tested on single chemically skinned cells isolated from rat ventricle. The present study demonstrates that (+)-EMD-57033 (10 microM) increased maximal force by 20% (at pCa 4.5) and myofilament Ca sensitivity by 0.2 pCa unit. However, the force-length dependency was not affected by the addition of (+)-EMD-57033, since similar Ca-sensitizing effects occurred at different sarcomere lengths. Consequently, the Ca-sensitizing effect of the drug and of the sarcomere length might be additive. Cross-bridge kinetics were also investigated in the presence of the thiadiazinone derivative. (+)-EMD-57033 induced marked increases in the rate of tension redevelopment (ktr) after brief slack release/restretch, particularly at low Ca concentrations. These results suggest that the Ca-sensitizing effects of (+)-EMD-57033 are due, at least in part, to an increased number of attached cross bridges during one cyclo. This observation, together with the increase in peak force, is discussed in relation to the reduction in energy cost induced by such Ca-sensitizing agents.
Vannier et al. (Thu,) studied this question.