The results demonstrate that selenite, through alterations of cellular thiol redox status, induced a dual action on muscle contraction that can be imputed to a combined action on Ca2+ channels, Ca2+ transporters and contractile proteins. Extracellular negative effects of selenite are due to a partial reduction of Ca2+ current magnitude. Intracellular effects are mediated both by a diminution of Ca2+ handing by intracellular organelles and by a sensitization of the contractile to Ca2+ ions. The results further indicate that selenite uptake into the cardiac cells occurs mainly through the temperature-sensitive anion exchanger.

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.

Objectives: The effects of Ca 2+ on the rate of tension redevelopment following a brief release/restretch were investigated in single chemically-skinned ventricular myocytes from the rat. Methods: The myocytes were enzymatically isolated and skinned using Triton-X100. They were then attached with an optical adhesive glue to glass micropipettes fixed to a piezoelectric translator and a force transducer. Tension redevelopment was measured at various levels of Ca activation after disrupting force-generating crossbridges by a brief (20 ms) step release/restretch equivalent to 20% of the original 2.1 Ixm sarcomere length. Most of tension redevelopment was well fitted by a monoexponential function. Results: At maximal Ca concentration, pCa 4.5 maximal force was obtained at 2.1 Ixm sarcomere length and averaged 11.8 +_ 0.7 p~N. The rate of tension redevelopment (kt~.) increased with increasing Ca concentrations up to 5.19 _+ 0.37 • s-1 at maximal Ca activation. The relation between the rate of tension redevelopment and Ca concentration was sigmoidal and could be fitted by the Hill equation with coefficients similar to those describing the tension-pCa relation. The relation between relative rate of tension redevelopment and relative steady activated tension was curvilinear increasing with increasing Ca concentration. Conclusions: In cardiac muscle, Ca 2+ modulates both the number and the kinetics of force-generating crossbridges in a manner similar to that previously reported in skeletal muscle.