Troponin C regulates the rate constant for the dissociation of force-generating myosin cross-bridges in cardiac muscle

Ying Wang, Yuanyuan Xu, Konrad Guth, W. Glenn Kerrick

Research output: Contribution to journalArticle

21 Citations (Scopus)

Abstract

It is well known that cardiac troponin C (cTnC) regulates the association of force-generating myosin cross-bridges. We report here evidence for an additional role for cTnC. This hypothesis states that Ca2+ binds more strongly to cTnC when force-generating myosin cross-bridges are attached to actin and that removal of this bound Ca2+ accelerates the dissociation of force-generating myosin cross-bridges. Intact Fura-2-loaded rat papillary muscles and skinned (permeabilized) ventricular preparations were used. The preparations were mounted in the Guth Muscle Research System which is capable of measuring simultaneously fluorescence and force in response to length perturbations. All mechanical perturbations of muscle length (isotonic shortening, quick stretches and releases, and length vibrations) which cause dissociation of force-generating myosin cross-bridges during a twitch resulted in Ca2+ being released from troponin as judged from changes in the Ca2+ transients (Fura-2 (340/380) fluorescence ratio). Thus dissociation of force-generating myosin cross-bridges cause Ca2+ to be released from cTnC. Conversely, it would be expected that removal of strongly bound Ca2+ from cTnC would result in an increase in the rate of dissociation of force-generating myosin cross-bridges. To test this hypothesis actomyosin ATPase (NADH fluorescence change) and isometric force were measured in skinned cardiac preparations. The ratio of the ATPase/Force is proportional to the rate constant (g(app)) for the dissociation of force-generating myosin cross-bridges. The data showed that decreasing the amount of Ca2+ bound to cTnC in skinned cardiac fibers caused an increase in the ratio of ATPase/Force, the rate of dissociation (g(app)) of force-generating myosin cross-bridges.

Original languageEnglish
Pages (from-to)645-653
Number of pages9
JournalJournal of Muscle Research and Cell Motility
Volume20
Issue number7
DOIs
StatePublished - Dec 1 1999

Fingerprint

Troponin C
Myosins
Muscle
Rate constants
Myocardium
Fura-2
Fluorescence
Application programs
Adenosine Triphosphatases
Muscles
Troponin
Papillary Muscles
Vibration
NAD
Rats
Actins
Association reactions

ASJC Scopus subject areas

  • Physiology
  • Clinical Biochemistry
  • Endocrinology
  • Cell Biology

Cite this

Troponin C regulates the rate constant for the dissociation of force-generating myosin cross-bridges in cardiac muscle. / Wang, Ying; Xu, Yuanyuan; Guth, Konrad; Kerrick, W. Glenn.

In: Journal of Muscle Research and Cell Motility, Vol. 20, No. 7, 01.12.1999, p. 645-653.

Research output: Contribution to journalArticle

@article{c52c45ddc3dc4975a8c012995572b3e0,
title = "Troponin C regulates the rate constant for the dissociation of force-generating myosin cross-bridges in cardiac muscle",
abstract = "It is well known that cardiac troponin C (cTnC) regulates the association of force-generating myosin cross-bridges. We report here evidence for an additional role for cTnC. This hypothesis states that Ca2+ binds more strongly to cTnC when force-generating myosin cross-bridges are attached to actin and that removal of this bound Ca2+ accelerates the dissociation of force-generating myosin cross-bridges. Intact Fura-2-loaded rat papillary muscles and skinned (permeabilized) ventricular preparations were used. The preparations were mounted in the Guth Muscle Research System which is capable of measuring simultaneously fluorescence and force in response to length perturbations. All mechanical perturbations of muscle length (isotonic shortening, quick stretches and releases, and length vibrations) which cause dissociation of force-generating myosin cross-bridges during a twitch resulted in Ca2+ being released from troponin as judged from changes in the Ca2+ transients (Fura-2 (340/380) fluorescence ratio). Thus dissociation of force-generating myosin cross-bridges cause Ca2+ to be released from cTnC. Conversely, it would be expected that removal of strongly bound Ca2+ from cTnC would result in an increase in the rate of dissociation of force-generating myosin cross-bridges. To test this hypothesis actomyosin ATPase (NADH fluorescence change) and isometric force were measured in skinned cardiac preparations. The ratio of the ATPase/Force is proportional to the rate constant (g(app)) for the dissociation of force-generating myosin cross-bridges. The data showed that decreasing the amount of Ca2+ bound to cTnC in skinned cardiac fibers caused an increase in the ratio of ATPase/Force, the rate of dissociation (g(app)) of force-generating myosin cross-bridges.",
author = "Ying Wang and Yuanyuan Xu and Konrad Guth and Kerrick, {W. Glenn}",
year = "1999",
month = "12",
day = "1",
doi = "10.1023/A:1005559613516",
language = "English",
volume = "20",
pages = "645--653",
journal = "Journal of Muscle Research and Cell Motility",
issn = "0142-4319",
publisher = "Springer Netherlands",
number = "7",

}

TY - JOUR

T1 - Troponin C regulates the rate constant for the dissociation of force-generating myosin cross-bridges in cardiac muscle

AU - Wang, Ying

AU - Xu, Yuanyuan

AU - Guth, Konrad

AU - Kerrick, W. Glenn

PY - 1999/12/1

Y1 - 1999/12/1

N2 - It is well known that cardiac troponin C (cTnC) regulates the association of force-generating myosin cross-bridges. We report here evidence for an additional role for cTnC. This hypothesis states that Ca2+ binds more strongly to cTnC when force-generating myosin cross-bridges are attached to actin and that removal of this bound Ca2+ accelerates the dissociation of force-generating myosin cross-bridges. Intact Fura-2-loaded rat papillary muscles and skinned (permeabilized) ventricular preparations were used. The preparations were mounted in the Guth Muscle Research System which is capable of measuring simultaneously fluorescence and force in response to length perturbations. All mechanical perturbations of muscle length (isotonic shortening, quick stretches and releases, and length vibrations) which cause dissociation of force-generating myosin cross-bridges during a twitch resulted in Ca2+ being released from troponin as judged from changes in the Ca2+ transients (Fura-2 (340/380) fluorescence ratio). Thus dissociation of force-generating myosin cross-bridges cause Ca2+ to be released from cTnC. Conversely, it would be expected that removal of strongly bound Ca2+ from cTnC would result in an increase in the rate of dissociation of force-generating myosin cross-bridges. To test this hypothesis actomyosin ATPase (NADH fluorescence change) and isometric force were measured in skinned cardiac preparations. The ratio of the ATPase/Force is proportional to the rate constant (g(app)) for the dissociation of force-generating myosin cross-bridges. The data showed that decreasing the amount of Ca2+ bound to cTnC in skinned cardiac fibers caused an increase in the ratio of ATPase/Force, the rate of dissociation (g(app)) of force-generating myosin cross-bridges.

AB - It is well known that cardiac troponin C (cTnC) regulates the association of force-generating myosin cross-bridges. We report here evidence for an additional role for cTnC. This hypothesis states that Ca2+ binds more strongly to cTnC when force-generating myosin cross-bridges are attached to actin and that removal of this bound Ca2+ accelerates the dissociation of force-generating myosin cross-bridges. Intact Fura-2-loaded rat papillary muscles and skinned (permeabilized) ventricular preparations were used. The preparations were mounted in the Guth Muscle Research System which is capable of measuring simultaneously fluorescence and force in response to length perturbations. All mechanical perturbations of muscle length (isotonic shortening, quick stretches and releases, and length vibrations) which cause dissociation of force-generating myosin cross-bridges during a twitch resulted in Ca2+ being released from troponin as judged from changes in the Ca2+ transients (Fura-2 (340/380) fluorescence ratio). Thus dissociation of force-generating myosin cross-bridges cause Ca2+ to be released from cTnC. Conversely, it would be expected that removal of strongly bound Ca2+ from cTnC would result in an increase in the rate of dissociation of force-generating myosin cross-bridges. To test this hypothesis actomyosin ATPase (NADH fluorescence change) and isometric force were measured in skinned cardiac preparations. The ratio of the ATPase/Force is proportional to the rate constant (g(app)) for the dissociation of force-generating myosin cross-bridges. The data showed that decreasing the amount of Ca2+ bound to cTnC in skinned cardiac fibers caused an increase in the ratio of ATPase/Force, the rate of dissociation (g(app)) of force-generating myosin cross-bridges.

UR - http://www.scopus.com/inward/record.url?scp=0033383559&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0033383559&partnerID=8YFLogxK

U2 - 10.1023/A:1005559613516

DO - 10.1023/A:1005559613516

M3 - Article

C2 - 10672512

AN - SCOPUS:0033383559

VL - 20

SP - 645

EP - 653

JO - Journal of Muscle Research and Cell Motility

JF - Journal of Muscle Research and Cell Motility

SN - 0142-4319

IS - 7

ER -