Abstract
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 (INa), high-voltage activated Ca2+ currents (ICa), or by a combination of the two. Previous computational models of pituitary cells have mainly been based on data from rats, where INa is largely inactivated at the resting potential, and spontaneous APs are predominantly mediated by ICa. Unlike in rats, spontaneous INa-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 INa, and (3) the first pituitary cell model where the kinetics of the depolarizing currents, INa and ICa, 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 ICa-based APs. We put a particular focus on how the big conductance K+ current (IBK) modulates the AP shape. Interestingly, we find that IBK can prolong AP duration in models that fire ICa-based APs, while it consistently shortens the duration of the predominantly INa-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 INa-mediated APs.
Highlights
Several types of excitable cells elicit electrical pulses called action potentials (APs), which, depending on cell type, can trigger neurotransmitter release, cellular contraction, hormone release or other actions
APs are generated by a combination of ion channels in the plasma membrane, which are typically characterized by the type of ions they are permeable to, and their voltage and/or Ca2+ dependent gating properties
The indication that there are differences between rat and fish pituitary cells are further supported by experiments presented in the current work, performed on luteinizing hormone (LH)-producing gonadotroph cells in medaka. We show that these cells elicit brief spontaneous APs that, unlike spontaneous APs in the previous murine pituitary cell models, predominantly are mediated by TTX sensitive Na+ currents (INa)
Summary
Several types of excitable cells elicit electrical pulses called action potentials (APs), which, depending on cell type, can trigger neurotransmitter release, cellular contraction, hormone release or other actions. The primary role of APs in endocrine pituitary cells is to regulate the cytosolic Ca2+ concentration, which in turn controls the hormone secretion rate in these cells [1]. Hormone secretion often occurs as a response to input from the hypothalamus, peripheral endocrine glands, or from other pituitary cells. Many endocrine cells are spontaneously active [1,2,3,4,5,6,7,8,9,10]. The spontaneous activity is partly a means to regulate the re-filling of intracellular Ca2+ stores, but in several cells leads to a basal release of hormones. An understanding of the mechanisms regulating the electrodynamics of these cells is fundamental for understanding their overall functioning
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