Abstract
We develop a point model of the cardiac myofilament (MF) to simulate
a wide variety of experimental muscle characterizations including
Force-Ca relations and twitches under isometric, isosarcometric,
isotonic, and auxotonic conditions. Complex MF behaviors are difficult
to model because spatial interactions cannot be directly implemented
as ordinary differential equations. We therefore allow phenomenological
approximations with careful consideration to the relationships with
the underlying biophysical mechanisms. We describe new formulations
that avoid mean-field approximations found in most existing MF models.
To increase the scope and applicability of the model, we include
length- and temperature-dependent effects that play important roles
in MF responses. We have also included a representation of passive
restoring forces to simulate isolated cell shortening protocols.
Possessing both computational efficiency and the ability to simulate
a wide variety of muscle responses, the MF representation is well
suited for coupling to existing cardiac cell models of electrophysiology
and Ca-handling mechanisms. To illustrate this suitability, the MF
model is coupled to the Chicago rabbit cardiomyocyte model. The combined
model generates realistic appearing action potentials, intracellular
Ca transients, and cell shortening signals. The combined model also
demonstrates that the feedback effects of force on Ca binding to
troponin can modify the cytosolic Ca transient.
Users
Please
log in to take part in the discussion (add own reviews or comments).