Effects of tropomyosin internal deletion Δ23Tm on isometric tension and the cross‐bridge kinetics in bovine myocardium

Direct action of the cardiotonic bipyridine milrinone on the cross bridges of single fibers of skinned rabbit skeletal muscle was investigated. At 10°C and pH 7.0, milrinone reduced isometric tension in a logarithmically concentration-dependent manner, with a 55% reduction in force at 0.6 mM. Milrinone also reduced Ca2+ sensitivity of skinned fibers in terms of force production; the shift in the force-pCa curve indicated a change in the pCa value at 50% maximal force from 6.10 to 5.94. The unloaded velocity of shortening was reduced by 18% in the presence of 0.6 mM milrinone. Parts of the transient tension response to step change in length were altered by milrinone, so that the test and control transients could not be superimposed. The results indicate that milrinone interferes with the cross-bridge cycle and possibly detains cross bridges in low-force states. The results also suggest that the positive inotropic effect of milrinone on cardiac muscle is probably not due to the drug’s direct action on the muscle cross bridges. The specific and reversible action of the bipyridine on muscle cross bridges makes it a potentially useful tool for probing the chemomechanical cross-bridge cycle.

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Temperature-Dependence of Isometric Tension and Cross-Bridge Kinetics of Cardiac Muscle Fibers Reconstituted with a Tropomyosin Internal Deletion Mutant

Biophysical Journal ◽

10.1529/biophysj.106.084608 ◽

2006 ◽

Vol 91 (11) ◽

pp. 4230-4240 ◽

Cited By ~ 14

Author(s):

Xiaoying Lu ◽

Larry S. Tobacman ◽

Masataka Kawai

Keyword(s):

Temperature Dependence ◽

Cardiac Muscle ◽

Deletion Mutant ◽

Muscle Fibers ◽

Isometric Tension ◽

Internal Deletion ◽

Cross Bridge ◽

Cardiac Muscle Fibers ◽

Kinetics Of

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BDM affects nucleotide binding and force generation steps of the cross-bridge cycle in rabbit psoas muscle fibers

AJP Cell Physiology ◽

10.1152/ajpcell.1994.266.2.c437 ◽

1994 ◽

Vol 266 (2) ◽

pp. C437-C447 ◽

Cited By ~ 29

Author(s):

Y. Zhao ◽

M. Kawai

Keyword(s):

Equilibrium Constants ◽

Muscle Fibers ◽

Psoas Muscle ◽

Isometric Tension ◽

Activation Mechanism ◽

Phosphate Binding ◽

Rabbit Psoas ◽

Cross Bridge ◽

The Cross ◽

Cross Bridges

The effect of 2,3-butanedione monoxime (BDM) on elementary steps of the cross-bridge cycle was studied with the sinusoidal analysis technique in skinned rabbit psoas muscle fibers. Our results showed that isometric tension and stiffness decreased progressively with an increase in the BDM concentration. The MgATP and MgADP binding constants increased 27 and 6 times, respectively, when BDM was increased from 0 to 18 mM, whereas the phosphate binding constant did not change significantly. The equilibrium constants of the ATP isomerization and detachment step were not sensitive to BDM, whereas the equilibrium constant of the attachment (power stroke) step decreased with BDM. Thus, in the presence of BDM, the number of attached cross bridges decreases; more cross bridges accumulate in the detached state, causing isometric tension and stiffness to decline. However, our detailed analysis shows that the decrease in the number of attached cross bridges is approximately 40%, which is not adequate to account for the 84% decrease in the isometric tension when 18 mM BDM was present. Therefore we suggest that a thin-filament activation mechanism is also affected by BDM.

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Isometric tension and instantaneous stiffness in amphibian skeletal muscle exposed to solutions of increased tonicity

Canadian Journal of Physiology and Pharmacology ◽

10.1139/y77-166 ◽

1977 ◽

Vol 55 (5) ◽

pp. 1208-1210 ◽

Cited By ~ 8

Author(s):

Bernard H. Bressler

Keyword(s):

Mechanical Response ◽

Current Model ◽

Ringer Solution ◽

Isometric Tension ◽

Bathing Solution ◽

Cross Bridge ◽

The Cross ◽

Cross Bridges ◽

Cross Bridge Mechanism ◽

Tetanic Tension

The instantaneous elasticity and maximum isometric tetanic tension of isolated frog and toad sartorii have been measured in hypertonic Ringer solution. Although the mechanical response of contracting muscle continued to decrease as the tonicity of the bathing solution was increased to 1.26 × R, 1.52 × R, and 2.04 × R, a similar change in the instantaneous stiffness could not be shown. This finding was not expected on the basis of our current model of the cross-bridge mechanism which predicts that the instantaneous stiffness is a measure of the total number of tension-generating cross-bridges formed in a stimulated muscle. The compatability of our findings with an electrostatic theory of the cross-bridge mechanism proposed by Iwazumi (1970) is discussed.

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Symmetric and Asymmetric Processes in the Mechano-Chemical Conversion in the Cross-Bridge Mechanism Studied by Isometric Tension Transients

Advances in Experimental Medicine and Biology - Contractile Mechanisms in Muscle ◽

10.1007/978-1-4684-4703-3_54 ◽

1984 ◽

pp. 585-599 ◽

Cited By ~ 1

Author(s):

H. Shimizu ◽

H. Tanaka

Keyword(s):

Chemical Conversion ◽

Isometric Tension ◽

Cross Bridge ◽

The Cross ◽

Cross Bridge Mechanism ◽

Tension Transients

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

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.1996.271.4.h1394 ◽

1996 ◽

Vol 271 (4) ◽

pp. H1394-H1406 ◽

Cited By ~ 6

Author(s):

Y. Zhao ◽

M. Kawai

Keyword(s):

Equilibrium Constant ◽

Isometric Tension ◽

Association Constants ◽

Phosphate Binding ◽

Sinusoidal Analysis ◽

Elementary Steps ◽

Cross Bridge ◽

The Cross ◽

Cross Bridges ◽

Emd 53998

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.

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