The effects of EMD 57033 on rigor tension in porcine skinned cardiac trabecula.
5-[1-(3,4-Dimethoxybenzoyl)-1,2,3,4-tetrahydro-6-quinolyl]-6-methy l-3,6- dihydro-2H-1,3,4-thiadiazin-2-one (EMD 57033) is a cardiotonic agent which acts directly on the myofilaments, increasing their sensitivity to Ca2+. We studied the effects of EMD 57033 on porcine cardiac skinned fibres to investigate the roles of Ca2+ and crossbridges in its Ca2+ sensitisation. EMD 57033 potentiated resting and maximum tensions and caused a leftward shift of the force-Ca2+ relationship. Under rigor conditions, in which fibres developed Ca(2+)-independent force, EMD 57033 was still able to potentiate tension, provided the compound was added prior to rigor development. These results show that EMD 57033 increases force by a Ca(2+)-independent mechanism in the intact myofilament lattice and that the Ca2+ sensitiser acts during the transition of crossbridge state rather than on crossbridges that are fixed in the strongly attached state corresponding to rigor.
Palmer
S
S
Research and Development, Pharmaceuticals Division, Ciba-Geigy Limited, Basel, Switzerland.
Di Bello
S
S
Herzig
J W
JW
D000255:Adenosine Triphosphate / Q000502:physiology; D000818:Animals; D002118:Calcium / Q000494:pharmacology; D002316:Cardiotonic Agents / Q000494:pharmacology*; D006321:Heart / Q000187:drug effects* / Q000294:innervation; D006352:Heart Ventricles / Q000166:cytology / Q000187:drug effects; D066298:In Vitro Techniques; D018485:Muscle Fibers, Skeletal / Q000187:drug effects / Q000502:physiology / Q000648:ultrastructure; D009186:Myelin Sheath / Q000502:physiology; D009200:Myocardial Contraction / Q000187:drug effects*; D009206:Myocardium / Q000166:cytology; D011804:Quinolines / Q000494:pharmacology*; D013552:Swine; D013829:Thiadiazines / Q000494:pharmacology*
D002316:Cardiotonic Agents; D011804:Quinolines; D013829:Thiadiazines; C070609:EMD 53998; D000255:Adenosine Triphosphate; D002118:Calcium