THE EFFECTS OF EMD-57033 ON RIGOR TENSION IN PORCINE SKINNED CARDIAC TRABECULA

yl]-6-methyl-3,6-dihydro-2H-1,3,4-thiadiazin-2-one (EMD 57033) is a ca rdiotonic agent which acts directly on the myofilaments, increasing th eir sensitivity to Ca2+. We studied the effects of EMD 57033 on porcin e cardiac skinned fibres to investigate the roles of Ca2+ and crossbri dges in its Ca2+ sensitisation. EMD 57033 potentiated resting and maxi mum tensions and caused a leftward shift of the force-Ca2+ relationshi p. Under rigor conditions, in which fibres developed Ca2+-independent force, EMD 57033 was still able to potentiate tension, provided the co mpound was added prior to rigor development. These results show that E MD 57033 increases force by a Ca2+-independent mechanism in the intact myofilament lattice and that the Ca2+ sensitiser acts during the tran sition of crossbridge state rather than on crossbridges that are fixed in the strongly attached state corresponding to rigor.