A CARDIAC-MUSCLE MODEL RELATING SARCOMERE DYNAMICS TO CALCIUM KINETICS

Citation
Ja. Negroni et Ec. Lascano, A CARDIAC-MUSCLE MODEL RELATING SARCOMERE DYNAMICS TO CALCIUM KINETICS, Journal of Molecular and Cellular Cardiology, 28(5), 1996, pp. 915-929
Citations number
31
Categorie Soggetti
Cardiac & Cardiovascular System
ISSN journal
00222828
Volume
28
Issue
5
Year of publication
1996
Pages
915 - 929
Database
ISI
SICI code
0022-2828(1996)28:5<915:ACMRSD>2.0.ZU;2-I
Abstract
A muscle model establishing the link between cross-bridge dynamics and intracellular Ca2+ kinetics was assessed by simulation of experiments performed in isolated cardiac muscle. The model is composed by the se ries arrangement of muscle units formed by inextensible thick and thin filaments in parallel with an elastic element. Attached cross-bridges act as independent force generators whose force is linearly related t o the elongation of their elastic structure. Ca2+ kinetics is describe d by a four-state system of sites on the thin filament associated with troponin C: sites with free troponin C (T), sites with Ca2+ bound to troponin C (TCa); sites with Ca2+ bound to troponin C and attached cro ss-bridges (TCa); and sites with troponin C not associated with Ca2and attached cross-bridges (T). The intracellular Ca2+ concentration ([Ca2+]) is controlled solely by the sarcoplasmic reticulum through an inflow function and a saturated outflow pump function. All the simula tions were performed using the same set of parameters. The model was a ble to reproduce the following experiments in cardiac muscle: (a) time course of isometric force (peak force: 46.5 mN/mm(2)), intracellular [Ca2+] (peak [Ca2+]: 1.5 mu M): (b) force-length-[Ca2+] relations; (c) transient response of force to step changes in length; (d) force-velo city relation (maximum velocity: 3 mu m/s); (e) the force response to length pulses to estimate the time course of [TCa]; (f) force response to quick releases showing the superactivating and deactivating effect s of shortening; (g) stiffness response to sinusoidal length changes; and (h) time course of active state. The good accordance of the simula tions with experimental results indicates that the model is an adequat e representation of the link between cross-bridge dyamic behaviour and Ca2+ kinetics. (C) 1996 Academic Press Limited