Inotropic agent EMD-53998 weakens nucleotide and phosphate binding to cross bridges in porcine myocardium

Yan Zhao; M Kawai

doi:10.1152/ajpheart.1996.271.4.H1394

Back

Inotropic agent EMD-53998 weakens nucleotide and phosphate binding to cross bridges in porcine myocardium

Journal article

Peer reviewed

Inotropic agent EMD-53998 weakens nucleotide and phosphate binding to cross bridges in porcine myocardium

Yan Zhao and M Kawai

The American journal of physiology, Vol.271(4 Pt 2), pp.H1394-H1406

10/1996

DOI: 10.1152/ajpheart.1996.271.4.H1394

PMID: 8897933

View Online

Abstract

The effect of EMD-53998 (EMD) on elementary steps of the cross-bridge cycle in skinned porcine myocardium was studied to understand the positive 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 microM EMD. In the presence of 50 microM 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 microM EMD, the association constants of MgATP and MgADP decrease to one-ninth and one-third, respectively, and the association constant of phosphate decreases to one-third. These results indicate that EMD suppresses the nucleotide binding to cross bridges and increases cross-bridge 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 twofold increase of isometric tension with 50 microM EMD.

Elasticity

Isometric Contraction - drug effects

Heart - physiology

Myocardial Contraction - drug effects

Dimethyl Sulfoxide - pharmacology

Cardiotonic Agents - pharmacology

Quinolines - pharmacology

Phosphates - metabolism

Animals

Time Factors

Adenosine Triphosphate - metabolism

Myocardium - metabolism

Heart - drug effects

Adenosine Diphosphate - metabolism

Contractile Proteins - metabolism

Thiadiazines - pharmacology

Details

Title: Subtitle: Inotropic agent EMD-53998 weakens nucleotide and phosphate binding to cross bridges in porcine myocardium
Creators: Yan Zhao - Department of Anatomy, University of Iowa, Iowa City 52242, USA
M Kawai
Resource Type: Journal article
Publication Details: The American journal of physiology, Vol.271(4 Pt 2), pp.H1394-H1406
Publisher: United States
DOI: 10.1152/ajpheart.1996.271.4.H1394
PMID: 8897933
ISSN: 0002-9513
eISSN: 2163-5773
Language: English
Date published: 10/1996
Academic Unit: Anatomy and Cell Biology; Internal Medicine
Record Identifier: 9984025326202771

Metrics

7 Record Views

25 Times Cited - Web of Science