The thiadiazinone EMD 57033 speeds the activation of skinned cardiac muscle produced by the photolysis of nitr-5.
EMD 57033 is thought to produce its potentiating effect by increasing the apparent Ca2+ sensitivity of the myofilaments, possibly by altering the kinetics of actomyosin interaction. We have investigated the effect of 10 microM EMD 57033 upon activation speed, induced by flash photolysis of 2mM nitr-5 (caged Ca2+), in chemically skinned trabeculae from the guinea-pig at 12 degrees C. EMD 57033 increases the half time of activation from 238 +/- 18.5 msec (n = 6) to 132.1 +/- 34.0 msec (n = 8) (mean +/- s.e.m.) and suggests that this Ca2+ sensitiser has an important effect upon fapp, that is the transition from the non-force to force generating cross-bridge states.
Simnett
S J
SJ
University Laboratory of Physiology, Oxford, UK.
Lipscomb
S
S
Ashley
C C
CC
Potter
J D
JD
Mulligan
I P
IP
D008841:Actin Cytoskeleton / Q000187:drug effects / Q000378:metabolism; D000818:Animals; D002118:Calcium / Q000378:metabolism; D002316:Cardiotonic Agents / Q000494:pharmacology*; D002614:Chelating Agents / Q000737:chemistry / Q000494:pharmacology*; D004533:Egtazic Acid / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology; D006168:Guinea Pigs; D006321:Heart / Q000187:drug effects*; D066298:In Vitro Techniques; D009200:Myocardial Contraction / Q000187:drug effects; D009206:Myocardium / Q000378:metabolism; D010782:Photolysis; D011804:Quinolines / Q000494:pharmacology*; D013829:Thiadiazines / Q000494:pharmacology*
D002316:Cardiotonic Agents; D002614:Chelating Agents; D011804:Quinolines; D013829:Thiadiazines; C052455:nitr 5; C070609:EMD 53998; D004533:Egtazic Acid; D002118:Calcium