Tension response of the cardiotonic agent (+) emd 57033 at the single cell level. Vannier, Catherine, Vladimir Lakomkine, and Guy Vassort. Laboratoire de Physiopathologie Cardiovasculaire, INSERM U-390, CHU Arnaud de Villeneuve, 34295 Montpellier, France
APStracts 3:0404C, 1996.
The effects of the calcium sensitizer (+) EMD 57033 were tested on single chemically skinned cells isolated from rat ventricle. The present study demonstrates that (+) EMD 57033 (10 [mu]M) increased maximal force by 20% (at pCa 4.5) and myofilament Ca sensitivity by 0.2 U.pCa. 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. Crossbridge 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 calcium sensitizing effects of (+) EMD 57033 are due, at least in part, to an increased number of attached crossbridges during one cycle. This observation together with the increase in peak force is discussed in relation with the reduction in energy cost induced by such Ca sensitizing agents.

Received 20 March 1996; accepted in final form 3 December 1996.
APS Manuscript Number C160-6.
Article publication pending Am. J. Physiol. (Cell Physiology).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 31 December 1996