Model Documentation

Model Status

This is the original unchecked version of the model imported from the previous CellML model repository, 24-Jan-2006.

Model Structure

Ca²⁺ flux through voltage-gated channels plays a role in muscle contraction, gene expression, synaptic transmission, short- and long-term memory. Ca²⁺ channels are regulated by many electrical, genetic and biochemical pathways, including G-protein signal transduction pathways. In their 2002 study, Richard Bertram, Michelle I. Arnot, and Gerald W. Zamponi focus on the direct regulation of N-type Ca²⁺ channels by the G-beta-gamma subunits of activated G-proteins (see the figure below). Ca²⁺ ion binding to a low-affinity binding site induces vesicle fusion with the plasma membrane, followed by the release of transmitter by exocytosis. Transmitter binding to a presynaptic autoreceptor activates a G-protein, the G-beta-gamma subunit od which binds directly to an N-type Ca²⁺ channel. Such binding puts channels into a reluctant state, reducing the net flow of Ca²⁺ into the cell. Autoinhibition of transmitter release then occurs as the result of the G-protein-mediated inhibition of Ca²⁺ channels. The resultant depolarisation results in the unbinding of G-beta-gamma from the channel.

The mathematical model developed by bertram et al. in this study was used to address two questions: 1) What is the role of G-protein-mediated autoinhibition on synaptic signalling processing; and 2) How is signal processing affected by different G-beta-gamma isoforms? The presynaptic model has equations for membrane potential, Ca²⁺-dependent transmitter release, transmitter binding to autoreceptors, and Ca²⁺ influx through G-protein-regulated channels. 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:

Role for G Protein G-Beta-Gamma Isoform Specificity in Synaptic Signal Processing: A Computational Study, Richard Bertram, Michelle I. Arnot, and Gerald W. Zamponi, 2002, Journal of Neurophysiology , 87, 2612-2623. (Full text and PDF versions of the article are available for Journal Members on the Journal of Neurophysiology website.) PubMed ID: 11976397

Schematic diagram of the presynaptic model.

G-protein autoinhibitory feedback on the presynaptic terminal acts like a high-pass filter, allowing only high-frequency signals to pass through the to the postsynaptic cell. Low-frequency signals are effectively filtered out. Model simulations in this study show how different G-beta-gamma isoforms have different filtering properties. They also emphasise that the different filtering characteristics associated with a specific G-beta-gamma subunit depend on many biophysical parameters, such as the unbinding rate of a transmitter molecule from the presynaptic autoreceptor. For example faster unbinding lowers the filter cut while slower unbinding raises it. This allows for great synapse-tot-synapse variability in the distinction between signal and background noise.

Related Models

• Role for G protein Gbetagamma isoform specificity in synaptic signal processing: a computational study version 4
• Role for G Protein G-beta-gamma Isoform Specificity in Synaptic Signal Processing: A Computational Study version 3
• Role for G Protein G-beta-gamma Isoform Specificity in Synaptic Signal Processing: A Computational Study version 2