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
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