The functions of anterior pituitary cells are controlled by two major groups of hypothalamic and intrapituitary ligands: one exclusively acts on G protein-coupled receptors and the other activates both G protein-coupled receptors and ligand-gated receptor channels. The second group of ligands operates as neurotransmitters in neuronal cells and their receptors are termed as neurotransmitter receptors. Most information about pituitary neurotransmitter receptors was obtained from secretory studies, RT-PCR analyses of mRNA expression and immunohistochemical and biochemical analyses, all of which were performed using a mixed population of pituitary cells. However, recent electrophysiological and imaging experiments have characterized γ-aminobutyric acid-, acetylcholine-, and ATP-activated receptors and channels in single pituitary cell types, expanding this picture and revealing surprising differences in their expression between subtypes of secretory cells and between native and immortalized pituitary cells. The main focus of this review is on the electrophysiological and pharmacological properties of these receptors and their roles in calcium signaling and calcium-controlled hormone secretion.

• Klíčová slova
• Action potentials, Calcium signaling, G protein-coupled receptors, Hormone secretion, Ligand-gated receptor channels, Neurotransmitters, Pituitary,
• MeSH
• buněčný rodokmen MeSH
• hormony adenohypofýzy metabolismus   MeSH
• lidé MeSH
• ligandy MeSH
• receptory neurotransmiterů metabolismus   MeSH
• signální transdukce * MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH
• Research Support, N.I.H., Intramural MeSH
• Názvy látek
• hormony adenohypofýzy MeSH
• ligandy MeSH
• receptory neurotransmiterů MeSH

Pituitary corticotrophs fire action potentials spontaneously and in response to stimulation with corticotropin-releasing hormone (CRH) and arginine vasopressin (AVP), and such electrical activity is critical for calcium signaling and calcium-dependent adrenocorticotropic hormone secretion. These cells typically fire tall, sharp action potentials when spontaneously active, but a variety of other spontaneous patterns have also been reported, including various modes of bursting. There is variability in reports of the fraction of corticotrophs that are electrically active, as well as their patterns of activity, and the sources of this variation are not well understood. The ionic mechanisms responsible for CRH- and AVP-triggered electrical activity in corticotrophs are also poorly characterized. We use electrophysiological measurements and mathematical modeling to investigate possible sources of variability in patterns of spontaneous and agonist-induced corticotroph electrical activity. In the model, variation in as few as two parameters can give rise to many of the types of patterns observed in electrophysiological recordings of corticotrophs. We compare the known mechanisms for CRH, AVP, and glucocorticoid actions and find that different ionic mechanisms can contribute in different but complementary ways to generate the complex time courses of CRH and AVP responses. In summary, our modeling suggests that corticotrophs have several mechanisms at their disposal to achieve their primary function of pacemaking depolarization and increased electrical activity in response to CRH and AVP.NEW & NOTEWORTHY We and others recently demonstrated that the electrical activity and calcium dynamics of corticotrophs are strikingly diverse, both spontaneously and in response to the agonists CRH and AVP. Here we demonstrate this diversity with electrophysiological measurements and use mathematical modeling to investigate its possible sources. We compare the known mechanisms of agonist-induced activity in the model, showing how the context of ionic conductances dictates the effects of agonists even when their target is fixed.

• Klíčová slova
• action potentials, corticotrophs, corticotropin-releasing hormone, ion channels, vasopressin,
• MeSH
• akční potenciály * MeSH
• arginin vasopresin metabolismus   MeSH
• hormon uvolňující kortikotropin metabolismus   MeSH
• iontové kanály metabolismus   MeSH
• kortikotropní buňky metabolismus   fyziologie   MeSH
• kultivované buňky MeSH
• modely neurologické * MeSH
• myši inbrední C57BL MeSH
• myši MeSH
• zvířata MeSH
• Check Tag
• mužské pohlaví MeSH
• myši MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• arginin vasopresin MeSH
• hormon uvolňující kortikotropin MeSH
• iontové kanály MeSH

Transgenic mice expressing the tdimer2(12) form of Discosoma red fluorescent protein under control of the proopiomelanocortin gene's regulatory elements are a useful model for studying corticotrophs. Using these mice, we studied the ion channels and mechanisms controlling corticotroph excitability. Corticotrophs were either quiescent or electrically active, with a 22-mV difference in the resting membrane potential (RMP) between the 2 groups. In quiescent cells, CRH depolarized the membrane, leading to initial single spiking and sustained bursting; in active cells, CRH further facilitated or inhibited electrical activity and calcium spiking, depending on the initial activity pattern and CRH concentration. The stimulatory but not inhibitory action of CRH on electrical activity was mimicked by cAMP independently of the presence or absence of arachidonic acid. Removal of bath sodium silenced spiking and hyperpolarized the majority of cells; in contrast, the removal of bath calcium did not affect RMP but reduced CRH-induced depolarization, which abolished bursting electrical activity and decreased the spiking frequency but not the amplitude of single spikes. Corticotrophs with inhibited voltage-gated sodium channels fired calcium-dependent action potentials, whereas cells with inhibited L-type calcium channels fired sodium-dependent spikes; blockade of both channels abolished spiking without affecting the RMP. These results indicate that the background voltage-insensitive sodium conductance influences RMP, the CRH-depolarization current is driven by a cationic conductance, and the interplay between voltage-gated sodium and calcium channels plays a critical role in determining the status and pattern of electrical activity and calcium signaling.

• MeSH
• akční potenciály účinky léků   MeSH
• AMP cyklický metabolismus   MeSH
• dibutyryl cyklický AMP farmakologie   MeSH
• hormon uvolňující kortikotropin farmakologie   MeSH
• iontové kanály metabolismus   MeSH
• kolforsin farmakologie   MeSH
• kortikotropní buňky účinky léků   metabolismus   fyziologie   MeSH
• kultivované buňky MeSH
• kyselina arachidonová farmakologie   MeSH
• membránové potenciály účinky léků   MeSH
• metoda terčíkového zámku MeSH
• myši inbrední C57BL MeSH
• myši transgenní MeSH
• sodík metabolismus   MeSH
• vápník metabolismus   MeSH
• vápníková signalizace účinky léků   MeSH
• vápníkové kanály - typ L metabolismus   MeSH
• zvířata MeSH
• Check Tag
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Research Support, N.I.H., Intramural MeSH
• Názvy látek
• AMP cyklický MeSH
• dibutyryl cyklický AMP MeSH
• hormon uvolňující kortikotropin MeSH
• iontové kanály MeSH
• kolforsin MeSH
• kyselina arachidonová MeSH
• sodík MeSH
• vápník MeSH
• vápníkové kanály - typ L MeSH