A Simple Mathematical Model of Second-Messenger Mediated Slow Excitatory

We have developed a novel and simple mathematical model of a slow excitatory postsynaptic potential ased on an abstraction of the processes of activation, inactivation, and summation of a cAMP, protein kinase A (PKA)-dependent second-messenger cascade. The model describes the activation of receptors, G-proteins, and production of cAMP as the first stage and uses first-order, non-rate-limited kinetics. The second stage corresponds to the release of active, PKA catalytic subunit and can use first- or higher-order kinetics. The third stage represents simple phosphorylation of ion channels and is limited by the number of channels available. The decay of each stage is based on first-order, mass-action kinetics. These equations and some variations were solved numerically and values of the parameters were determined by fitting to a variety of experimental data from myenteric neurons of the guinea-pig ileum. The model produced a slow EPSP with a nonlinear stimulus-response relationship that re...

• Type: Journal
• Year: 2000
• Where: JCNS
• Authors: P. P. Bertrand, E. A. Thomas, W. A. A. Kunze, J. C. Bornstein
• Keywords: Excitatory Postsynaptic Potential, JCNS 2000, Non-rate-limited Kinetics, Simple Mathematical Model