A computational model for gonadotropin releasing cells in the teleost fish medaka

Abstract

Pituitary endocrine cells fire action potentials (APs) to regulate their cytosolic Ca ²⁺ 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 Ca ²⁺ 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 predominantly mediated by I _Ca . 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 a computational model of gonadotropin releasing cells in the teleost fish medaka ( Oryzias latipes). The model stands out from previous modeling efforts by being (1) the first model of a pituitary cell in teleosts, (2) the first pituitary cell model that fires sponateous APs that are predominantly mediated by I _Na , and (3) the first pituitary cell model where the kinetics of the depolarizing currents, I _Na and I _Ca , are directly fitted to voltage-clamp data. We explore the firing properties of the model, and compare it to the properties of previous models that fire I _Ca -based APs. We put a particular focus on how the big conductance K ⁺ current ( I _BK ) modulates the AP shape. Interestingly, we find that I _BK can prolong AP duration in models that fire I _Ca -based APs, while it consistently shortens the duration of the predominantly I _Na -mediated APs in the medaka gonadotroph model. Although the model is constrained to experimental data from gonadotroph cells in medaka, it may likely provide insights also into other pituitary cell types that fire I _Na -mediated APs.

Author summary

Excitable cells elicit electrical pulses called action potentials (APs), which are generated and shaped by a combination of ion channels in the cell membrane. Since one type of ion channels is permeable to Ca ²⁺ ions, there is typically an influx of Ca ²⁺ during an AP. Pituitary cells therefore use AP firing to regulate their cytosolic Ca ²⁺ concentration, which in turn controls their hormone secretion rate. The amount of Ca ²⁺ that enters during an AP depends strongly on how long it lasts, and it is therefore important to understand the mechanisms that control this. Pituitary APs are generally mediated by a combination of Ca ²⁺ channels and Na ⁺ channels, and the relative contributions of from the two vary between cell types, animal species and biological conditions. Previous computer models have predominantly been adapted to data from pituitary cells which tend to fire Ca ²⁺-based APs. Here we develop a new model, adapted to data from pituitary cells in the fish medaka, which APs that are predominantly Na ⁺-based, and compare its dynamical properties to the previous models that fire Ca ²⁺-based APs.