2016 Conference on Computational Modelling with COPASI
Manchester Institute of Biotechnology, 12th – 13th May, 2016
1 - Babraham Institute, Cambridge, UK
Keywords: signalling, calcium, calmodulin, allostery, neuron, synaptic long-term potentiation, synaptic long-term depression
Common forms of short-term synaptic plasticities are associated with non-linear responses to calcium increases in the post-synaptic compartment. Calmodulin, one of the main calcium sensors in eukaryotic cells, is a small protein that carries four calcium binding sites with different affinities. Allostery and thermodynamic linkage explains many Calmodulin's properties, in particular the apparent increasing calcium affinity with fractional occupancy, the activity of non-saturated forms of calmodulin, and the increase in calcium affinity once calmodulin is bound to a target. Different conformations of calmodulin binds various targets with different affinities. These properties of calmodulin may suffice to explain the differential activation of calcineurin, leading to synaptic long-term depression, and calcium/calmodulin kinase II, leading to synaptic long-term potentiation. This also provides an explanation for the role of Neurogranin as a Calmodulin buffer, regulating availability of Calmodulin depending on calcium concentrations. Allosteric models can be embedded in models of biochemical pathways to study the kinetics of responses to calcium. Finally, such models can be integrated with electrophysiological models at the level of the entire neuron.