Albrecht, Colegrove, Friel, 2002

Model Status

This model is consistently represented within the CellML but contains sets of algebraic equations that prevent the model from being solved in currently available software - 03/08.

ValidateCellML found unit inconsistencies in this model

Model Structure

Calcium is an important signalling ion, and changes in Ca²⁺ concentration ([Ca²⁺]) regulate diverse processes in many cellular compartments. In excitable cells, depolarisation-induced Ca²⁺ entry increases [Ca²⁺]_i, leading to secondary changes in [Ca²⁺] within organelles such as mitochondria and ER that regulate specific Ca²⁺-sensitive targets within these organelles. Although mitochondria accumulate Ca²⁺ in response to depolarisation-evoked [Ca²⁺]_i elevations (see The Colegrove et al Model Of Mitochondrial Ca²⁺ Uptake And Release, 2000), the ER is also an important component in Ca²⁺ signalling in virtually all non-muscle cells, and it has been described as either a Ca²⁺ source or sink. Different modes of net ER Ca²⁺ transport are expected to have very different effects on cytoplasmic and intraluminal Ca²⁺ signals and on the processes they regulate (see The Albrecht et al Model Of Multiple Modes of Ca²⁺-induced Ca²⁺ Release in Sympathetic Neurons, 2001).

In a follow up study to their 2001 paper, Meredith A. Albrecht, Stephen L. Colegrove and David D. Friel have examined how differential regulation of ER Ca²⁺ uptake and release rates accounts for multiple modes of Ca²⁺-induced Ca²⁺ release. Three different macroscopic Ca²⁺ fluxes were modelled: J_SERCA, the rate of Ca²⁺ uptake via SR Ca-ATPases; J_ICa, the total cytoplasmic Ca²⁺ flux when SR Ca-ATPases are inhibited; and J_pm, the rate of Ca²⁺ extrusion across the plasma membrane. One additional flux J_release was calculated from the difference between J_ICa and J_pm (see the figure below). This mathematical model has been translated into a CellML description which can be downloaded in various formats as described in .

The complete original paper reference is cited below:

Differential Regulation of ER Ca²⁺ Uptake and Release Rates Accounts for Multiple Modes of Ca²⁺-induced Ca²⁺ Release, Meredith A. Albrecht, Stephen L. Colegrove and David D. Friel, 2002, The Journal Of General Physiology , 119, 211-233. (Full text and PDF versions of the article are available for Journal Members on the JGP website.) PubMed ID: 11865019

Schematic of the model indicating Ca2+ compartmentation in the extracellular matrix, cytosol and the ER and pathways for Ca2+ ion movement between the compartments.