Abstract
We have developed a detailed mathematical model for Ca$^2+$ handling
and ionic currents in the rabbit ventricular myocyte. The objective
was to develop a model that: 1), accurately reflects Ca-dependent
Ca release; 2), uses realistic parameters, particularly those that
concern Ca transport from the cytosol; 3), comes to steady state;
4), simulates basic excitation-contraction coupling phenomena; and
5), runs on a normal desktop computer. The model includes the following
novel features: 1), the addition of a subsarcolemmal compartment
to the other two commonly formulated cytosolic compartments (junctional
and bulk) because ion channels in the membrane sense ion concentrations
that differ from bulk; 2), the use of realistic cytosolic Ca buffering
parameters; 3), a reversible sarcoplasmic reticulum (SR) Ca pump;
4), a scheme for Na-Ca exchange transport that is Nai dependent
and allosterically regulated by Cai; and 5), a practical model
of SR Ca release including both inactivation/adaptation and SR Ca
load dependence. The data describe normal electrical activity and
Ca handling characteristics of the cardiac myocyte and the SR Ca
load dependence of these processes. The model includes a realistic
balance of Ca removal mechanisms (e.g., SR Ca pump versus Na-Ca exchange),
and the phenomena of rest decay and frequency-dependent inotropy.
A particular emphasis is placed upon reproducing the nonlinear dependence
of gain and fractional SR Ca release upon SR Ca load. We conclude
that this model is more robust than many previously existing models
and reproduces many experimental results using parameters based largely
on experimental measurements in myocytes.
- 15347581
- action
- animals,
- calcium
- calcium,
- cardiac,
- cardiovascular,
- cell
- computer
- contraction,
- gov't,
- heart
- humans,
- membrane
- membrane,
- models,
- myocardial
- myocytes,
- non-u.s.
- p.h.s.,
- potentials,
- research
- reticulum,
- sarcoplasmic
- signaling,
- simulation,
- support,
- u.s.
- ventricles,
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