Common and diverse elements of ion channels and receptors underlying electrical activity in endocrine pituitary cells

• Published in: Molecular and cellular endocrinology 2018-03, Vol.463, p.23-36
• Main Authors: Fletcher, Patrick A., Sherman, Arthur, Stojilkovic, Stanko S.
• Format: Article
• Language: English
• Subjects: Action potentials; Animals; calcium channels; Calcium signaling; Electrophysiological Phenomena; Endocrine Cells - metabolism; G-protein coupled receptors; gene expression regulation; hormone secretion; hormones; Hormones - metabolism; Humans; Ion channels; Ion Channels - metabolism; Mathematical modeling; mathematical models; pituitary gland; Pituitary Gland - cytology; Pituitary Gland - metabolism; Receptors, G-Protein-Coupled - metabolism; Voltage-gated calcium influx
• ISSN: 0303-7207; 1872-8057
• DOI: 10.1016/j.mce.2017.06.022

The pituitary gland contains six types of endocrine cells defined by hormones they secrete: corticotrophs, melanotrophs, gonadotrophs, thyrotrophs, somatotrophs, and lactotrophs. All these cell types are electrically excitable, and voltage-gated calcium influx is the major trigger for their hormone secretion. Along with hormone intracellular content, G-protein-coupled receptor and ion channel expression can also be considered as defining cell type identity. While many aspects of the developmental and activity dependent regulation of hormone and G-protein-coupled receptor expression have been elucidated, much less is known about the regulation of the ion channels needed for excitation-secretion coupling in these cells. We compare the spontaneous and receptor-controlled patterns of electrical signaling among endocrine pituitary cell types, including insights gained from mathematical modeling. We argue that a common set of ionic currents unites these cells, while differential expression of another subset of ionic currents could underlie cell type-specific patterns. We demonstrate these ideas using a generic mathematical model, showing that it reproduces many observed features of pituitary electrical signaling. Mapping these observations to the developmental lineage suggests possible modes of regulation that may give rise to mature pituitary cell types. •Pituitary cell type-specific electrical activity determines the pattern of basal and receptor-regulated exocytosis.•The relative amount of expressed ionic currents is critical to electrical activity patterns.•Mathematical modeling and experiments suggest expression of a common set of ion channels among pituitary cells.•Differential expression of a few additional channels is sufficient to explain cell type-specific activity patterns.•Developmental gain or loss of expression of specific ion channels and receptors is suggested to contribute to cell differentiation.