Analysis of a reduced model of corticotroph action potentials.

We have previously described a model for corticotroph plasma membrane electrophysiology [LeBeau et al. (1997). Biophysical Journal 73, 1263-1275]. The model is a Hodgkin-Huxley-like formalism consisting of six coupled ordinary differential equations. Analysis of this model showed that Ca2+ action potentials could be induced by an increase in the L-type voltage-sensitive Ca2+ current. Thus we have demonstrated a putative causal link between an increase in the corticotroph Ca2+ current and action potential generation. We report here the reduction of the model to one with three equations, the behaviour of which was found to correspond well with that of the full model. The reduced model was then subjected to fast-slow subsystem analysis, which revealed the mechanistic interaction between the membrane potential and intracellular Ca2+ concentration that underlies action potential generation. Insights obtained from this analysis were used to investigate experimentally observed aspects of corticotroph electrophysiology such as spontaneous electrical activity, bursting action potentials, and observations from anode break excitation experiments.