Mechanism of spontaneous and receptor-controlled electrical activity in pituitary somatotrophs:experiments and theory

KT Tsaneva-Atanasova, A Sherman, F van Goor, S Stojilkovic

Research output: Contribution to journalArticle (Academic Journal)peer-review

74 Citations (Scopus)

Abstract

Cultured pituitary somatotrophs release growth hormone in response to spontaneous Ca2+ entry through voltage-gated calcium channels (VGCCs) that is governed by plateau-bursting electrical activity and is regulated by several neurohormones, including GH-releasing hormone (GHRH) and somatostatin. Here we combine experiments and theory to clarify the mechanisms underlying spontaneous and receptor-controlled electrical activity. Experiments support a role of a Na+-conducting and tetrodotoxin-insensitive channel in controlling spontaneous and GHRH-stimulated pacemaking, the latter in a cAMP-dependent manner; an opposing role of spontaneously active inwardly rectifying K+ (Kir) channels and G-protein-regulated Kir channels in somatostatin-mediated inhibition of pacemaking; as well as a role of VGCCs in spiking and large conductance (BK-type) Ca2+-activated K+ channels in plateau bursting. The mathematical model is compatible with a wide variety of experimental data involving pharmacology and extracellular ion substitution and supports the importance of constitutively active tetrodotoxin-insensitive Na+ and Kir channels in maintaining spontaneous pacemaking in pituitary somatotrophs. The model also suggests that these channels are involved in the up- and downregulation of electrical activity by GHRH and somatostatin. In the model, the plateau bursting is controlled by two functional populations of BK channels, characterized by distance from the VGCCs. The rapid activation of the proximal BK channels is critical for the establishment of the plateau, whereas slow recruitment of the distal BK channels terminates the plateau.
Translated title of the contributionMechanism of spontaneous and receptor-controlled electrical activity in pituitary somatotrophs:experiments and theory
Original languageEnglish
Pages (from-to)131 - 144
Number of pages14
JournalJournal of Neurophysiology
Volume98
DOIs
Publication statusPublished - Jul 2007

Bibliographical note

Publisher: The American Physiological Society

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