The inward rectifier in a model of corticotroph electrical activity

Pituitary corticotroph cells generate repetitive action potentials and associated Ca2+ transients in response to the agonist corticotropin releasing hormone (CRH). There is indirect evidence suggesting that the agonist, by way of complex intracellular mechanisms, modulates the voltage sensitivity of the L-type Ca2+ channels embedded in the plasma membrane. We have previously constructed a Hodgkin–Huxley type model of this process, which indicated that an increase in the L-type Ca2+ current is sufficient to generate repetitive action potentials [LeBeau et al. (1997). Biophysical Journal 73, 1263–1275]. The agonist is also believed to inhibit an inwardly rectifying K+ current. In this paper we investigate a role of the inwardly rectifying K+ current in the action potential firing frequency and membrane excitability. We have found that a CRH-induced inhibition of the inwardly rectifying K+ current increases the action potential firing frequency and membrane excitability. This structural alter-ation to the model along with parametric changes bring the model firing frequency in line with experimental data. We also show that the model exhibits experimen-tally observed bursting behaviour, where the depolarization spike is followed by small oscillations in the membrane potential