Roux, Noble, Noble, Marhl, 2006

Model Status

This CellML model runs in both COR and PCEnv however the model does not replicate the published results. The units have been checked and are consistent. The original model author is working with us on the process of curation and we soon hope to have the CellML model running to replicate the published results.

Model Structure

Abstract: Airway myocytes are the primary effectors of airway reactivity which modulates airway resistance and hence ventilation. Stimulation of airway myocytes results in an increase in the cytosolic Ca2+ concentration ([Ca2+]i) and the subsequent activation of the contractile apparatus. Many contractile agonists, including acetylcholine, induce [Ca2+]i increase via Ca2+ release from the sarcoplasmic reticulum through InsP3 receptors. Several models have been developed to explain the characteristics of InsP3-induced [Ca2+]i responses, in particular Ca2+ oscillations. The article reviews the modelling of the major structures implicated in intracellular Ca2+ handling, i.e., InsP3 receptors, SERCAs, mitochondria and Ca2+-binding cytosolic proteins. We developed theoretical models specifically dedicated to the airway myocyte which include the major mechanisms responsible for intracellular Ca2+ handling identified in these cells. These biocomputations pointed out the importance of the relative proportion of InsP3 receptor isoforms and the respective role of the different mechanisms responsible for cytosolic Ca2+ clearance in the pattern of [Ca2+]i variations. We have developed a theoretical model of membrane conductances that predicts the variations in membrane potential and extracellular Ca2+ influx. Stimulation of this model by simulated increase in [Ca2+]i predicts membrane depolarisation, but not great enough to trigger a significant opening of voltage-dependant Ca2+ channels. This may explain why airway contraction induced by cholinergic stimulation does not greatly depend on extracellular calcium. The development of such models of airway myocytes is important for the understanding of the cellular mechanisms of airway reactivity and their possible modulation by pharmacological agents.

The complete original paper reference is cited below:

Modelling of calcium handling in airway myocytes, Etienne Roux, Penelope J. Noble, Denis Noble and Marko Marhl, 2006, Progress in Biophysics and Molecular Biology , 15, 556-565. (Full text and PDF versions of the article are available to journal subscribers on the Progress in Biophysics and Molecular Biology website.) PubMed ID: 15982722

Schematic diagram of the cell model. The model includes L-type voltage-operated Ca2+ current (ICaL), Ca2+-activated Cl- current (IClCa), Ca2+-activated K+ current (IKCa), delayed rectifier K+ current (IKdr), non-specific cationic current (Icationic), basal currents for Ca2+, Na+ and K+, the plasma membrane Ca2+ ATPase (PMCA) and the Na+-K+ATPase (NKA). Extracellular and intracellular concentrations of Na+, K+, Ca2+ and Cl- are fixed or forced.