Modelling and measuring electromechanical coupling in the rat heart.
Tension-dependent binding of Ca(2+) to troponin C in the cardiac myocyte has been shown to play an important role in the regulation of Ca(2+) and the activation of tension development. The significance of this regulatory mechanism is quantified experimentally by the quantity of Ca(2+) released following a rapid change in the muscle length. Using a computational, coupled, electromechanics cell model, we have confirmed that the tension dependence of Ca(2+) binding to troponin C, rather than cross-bridge kinetics or the rate of Ca(2+) uptake by the sarcoplasmic reticulum, determines the quantity of Ca(2+) released following a length step. This cell model has been successfully applied in a continuum model of the papillary muscle to analyse experimental data, suggesting the tension-dependent binding of Ca(2+) to troponin C as the likely pathway through which the effects of localized impaired tension generation alter the Ca(2+) transient. These experimental results are qualitatively reproduced using a three-dimensional coupled electromechanics model. Furthermore, the model predicts that changes in the Ca(2+) transient in the viable myocardium surrounding the impaired region are amplified in the absence of tension-dependent binding of Ca(2+) to troponin C.
Niederer
S A
SA
University Computing Laboratory, University of Oxford, Oxford, UK.
Ter Keurs
H E D J
HE
Smith
N P
NP
D000818:Animals; D020013:Calcium Signaling; D055724:Electrophysiological Phenomena; D006321:Heart / Q000502:physiology*; D008955:Models, Cardiovascular; D009200:Myocardial Contraction / Q000502:physiology; D032383:Myocytes, Cardiac / Q000502:physiology; D010210:Papillary Muscles / Q000502:physiology; D051381:Rats; D012519:Sarcoplasmic Reticulum / Q000378:metabolism; D019209:Troponin C / Q000378:metabolism
D019209:Troponin C