Pituitary endocrine cells fire action potentials (APs) to regulate their cytosolic Ca2+ concentration and hormone secretion rate. Depending on animal species, cell type, and biological conditions, pituitary APs are generated either by TTX-sensitive Na+ currents (I_Na), high-voltage activated Ca2+ currents (I_Ca), or by a combination of the two. Previous computational models of pituitary cells have mainly been based on data from rats, where I_Na is largely inactivated at the resting potential, and spontaneous APs are exclusively mediated by I_Ca. As a part of the previous modeling studies, a paradoxical role was identified for the big conductance K+ current (I_BK), which was found to prolong the duration of I_Ca-mediated APs, and sometimes give rise to pseudo-plateau bursts, contrary to what one would expect from a hyperpolarizing current. Unlike in rats, spontaneous I_Na-mediated APs are consistently seen in pituitary cells of several other animal species, including several species of fish. In the current work we develop the, to our knowledge, first computational model of a pituitary cell that fires I_Na-mediated APs. Although we constrain the model to experimental data from gonadotrope cells in the teleost fish medaka (Oryzias latipes), it may likely provide insights also into other pituitary cell types that fire I_Na-mediated APs. In the current work, we use the model to explore how the effect of I_BK depends on the AP generating mechanisms of pituitary cells. We do this by comparing simulations on the medaka gonadotrope model (two versions thereof) with simulations on a previously developed model of a rat pituitary cell. Interestingly, we find that I_BK has the opposite effect on APs in the two models, i.e. it reduces the duration of already fast I_Na-mediated APs in the medaka model, and prolongs the duration of already slow I_Ca-mediated APs in the rat model.

BK channels have opposite effects on sodium versus calcium-mediated action potentials in endocrine pituitary cells.