Positive inotropic agent emd 53998 weakens nucleotide and phosphate
binding to cross-bridges in skinned porcine myocardium.
Zhao, Yan, and Masataka Kawai.
Department of Anatomy, The University of Iowa, Iowa city, IA
52242
APStracts 3:0092H, 1996.
The effect of EMD 53998 on elementary steps of the cross-bridge cycle
in skinned porcine myocardium was studied to understand the inotropic
mechanisms of EMD. The kinetic constants of the elementary steps were
obtained by sinusoidal analysis and compared in the presence and
absence of 50 [mu]M EMD 53998. In the presence of 50 [mu]M EMD, the
equilibrium constant of the cross-bridge detachment step decreases
three times, and the equilibrium constant of the cross-bridge
attachment (force generation) step increases two times. Our results
further show that in the presence of 50 [mu]M EMD, the association
constants of MgATP and MgADP decrease to 1/9 and 1/3, respectively,
and the association constant of phosphate decreases to 1/3. These
results indicate that EMD suppresses the nucleotide binding to cross
-bridges and increases the cross-bridge's resistance to phosphate
accumulation in myocardium. These results predict that EMD decreases
the number of detached cross-bridges, and increases the number of
attached cross-bridges. This prediction is consistent with the 2 fold
increase of isometric tension with 50 [mu]M EMD.
Received 31 July 1995; accepted in final form 26 February 1996.
APS Manuscript Number H717-5.
Article publication pending Am. J. Physiol. (Heart Circ. Physiology).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 13 March 96