[Ca2+]i oscillations in sympathetic neurons: an experimental test of a theoretical model
Catherine
Lloyd
Auckland Bioengineering Institute, The University of Auckland
Model Status
This CellML model runs in OpenCell and COR but unfortuntately does not recreate the published figures. The CellML model does not spontaneously oscillate.
Model Structure
ABSTRACT: [Ca2+]i oscillations have been described in a variety of cells. This study focuses on caffeine-induced [Ca2+]i oscillations in sympathetic neurons. Previous work has shown that these oscillations require Ca2+ entry from the extracellular medium and Ca(2+)-induced Ca2+ release from a caffeine- and ryanodine-sensitive store. The aim of the study was to understand the mechanism responsible for the oscillations. As a starting point, [Ca2+]i relaxations were examined after membrane depolarization and exposure to caffeine. For both stimuli, post-stimulus relaxations could be described by the sum of two decaying exponential functions, consistent with a one-pool system in which Ca2+ transport between compartments is regulated by linear Ca2+ pumps and leaks. After modifying the store to include a [Ca2+]i-sensitive leak, the model also exhibits oscillations such as those observed experimentally. The model was tested by comparing measured and predicted net Ca2+ fluxes during the oscillatory cycle. Three independent fluxes were measured, describing the rates of 1) Ca2+ entry across the plasma membrane, 2) Ca2+ release by the internal store, and 3) Ca2+ extrusion across the plasma membrane and uptake by the internal store. Starting with estimates of the model parameters deduced from post-stimulus relaxations and the rapid upstroke, a set of parameter values was found that provides a good description of [Ca2+]i throughout the oscillatory cycle. With the same parameter values, there was also good agreement between the measured and simulated net fluxes. Thus, a one-pool model with a single [Ca2+]i-sensitive Ca2+ permeability is adequate to account for many of the quantitative properties of steady-state [Ca2+]i oscillations in sympathetic neurons. Inactivation of the intracellular Ca2+ permeability, cooperative nonlinear Ca2+ uptake and extrusion mechanisms, and functional links between plasma membrane Ca2+ transport and the internal store are not required.
The original paper reference is cited below:
[Ca2+]i oscillations in sympathetic neurons: an experimental test of a theoretical model, David D. Friel, 1995, Biophysical Journal, 68, 1752-1766. PubMed ID: 7612818
cell schematic for the model
Schematic of the model indicating Ca2+ compartmentalization in the extracellular matrix, cytosol and the mitochondrial matrix and pathways for Ca2+ ion movement between the compartments.
$\mathrm{kappa\_L1}=\begin{cases}0.000005 & \text{if $(\mathrm{time}\ge 0)\land (\mathrm{time}< 30)$}\\ 0.00002 & \text{otherwise}\end{cases}\mathrm{kappa\_L2}=\mathrm{kappa\_L2\_0}+\frac{\mathrm{kappa\_L2\_1}}{1+\left(\frac{\mathrm{Kd\_Ca}}{\mathrm{Ca\_i}}\right)^{n}}\mathrm{Kd\_Ca}=\begin{cases}1.0 & \text{if $(\mathrm{time}\ge 0)\land (\mathrm{time}< 60)$}\\ 0.5 & \text{otherwise}\end{cases}$
$\frac{d \mathrm{Ca\_i}}{d \mathrm{time}}=\mathrm{kappa\_L1}+\mathrm{kappa\_P1}+\mathrm{gamma}(\mathrm{kappa\_L2}+\mathrm{kappa\_P2})\mathrm{Ca\_i}+\mathrm{gamma}\mathrm{kappa\_L2}\mathrm{Ca\_s}+\mathrm{kappa\_L1}\mathrm{Ca\_o}\mathrm{Ca\_i\_ss}=\frac{\mathrm{Ca\_o}}{1.0+\frac{\mathrm{kappa\_P1}}{\mathrm{kappa\_L1}}}$
$\frac{d \mathrm{Ca\_s}}{d \mathrm{time}}=(\mathrm{kappa\_L2}+\mathrm{kappa\_P2})\mathrm{Ca\_i}-\mathrm{kappa\_L2}\mathrm{Ca\_s}\mathrm{Ca\_s\_ss}=\mathrm{Ca\_i\_ss}(1.0+\frac{\mathrm{kappa\_P2}}{\mathrm{kappa\_L2}})$
[Ca2+]i oscillations in sympathetic neurons: an experimental test of a theoretical model
1752176668Biophysical Journal
This is the CellML description of David Friel's 1995 model of calcium
oscillations in sympathetic neurons.
neurobiologysympatheticelectrophysiologyneuroncalcium dynamics76128182002-07-22
Added more metadata.
The University of Auckland, Auckland Bioengineering Institute
CuellarAutumnAFrielDavidDLloydCatherineMayCatherine Lloyd
A Model Of Calcium Oscillations in Sympathetic Neurons
Sympathetic Neuronkeyword
Added publication date information.
c.lloyd@auckland.ac.nzAuckland Bioengineering InstituteThe University of Auckland0.110000falsetruebdf153002003-04-09LloydCatherineMay1995-052002-04-02