| | Models | Description |
| 1. |
A model for pituitary GH(3) lactotroph (Wu and Chang 2005)
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The ATP-sensitive K(+) (K(ATP)) channels are composed of sulfonylurea receptor and inwardly rectifying K(+) channel (Kir6.2) subunit. These channels are regulated by intracellular ADP/ATP ratio and play a role in cellular metabolism. ... The objective of this study was to determine whether Diethyl pyrocarbonate (DEPC) modifies K(ATP)-channel activity in pituitary GH(3) cells. ... Simulation studies also demonstrated that the increased conductance of K(ATP)-channels used to mimic DEPC actions reduced the frequency of spontaneous action potentials and fluctuation of intracellular Ca(2+). The results indicate that chemical modification with DEPC enhances K(ATP)-channel activity and influences functional activities of pituitary GH(3) cells. See paper for more and details. |
| 2. |
BK - CaV coupling (Montefusco et al. 2017)
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An implementation of coupling between BK_Ca channels and CaV channels suitable for use in whole cell models. |
| 3. |
BK Channels Promote Bursting in Pituitary Cells (Tabak et al 2011)
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"The electrical activity pattern of endocrine pituitary cells regulates their basal secretion level. Rat somatotrophs and lactotrophs exhibit spontaneous bursting and have high basal levels of hormone secretion, while gonadotrophs exhibit spontaneous spiking and have low basal hormone secretion. It has been proposed that the difference in electrical activity between bursting somatotrophs and spiking gonadotrophs is due to the presence of large conductance potassium (BK) channels on somatotrophs but not on gonadotrophs. This is one example where the role of an ion channel type may be clearly established. We demonstrate here that BK channels indeed promote bursting activity in pituitary cells. Blocking BK channels in bursting lacto-somatotroph GH4C1 cells changes their firing activity to spiking, while further adding an artificial BK conductance via dynamic clamp restores bursting. Importantly, this burst-promoting effect requires a relatively fast BK activation/deactivation, as predicted by computational models. We also show that adding a fast-activating BK conductance to spiking gonadotrophs converts the activity of these cells to bursting. Together, our results suggest that differences in BK channel expression may underlie the differences in electrical activity and basal hormone secretion levels among pituitary cell types and that the rapid rate of BK channel activation is key to its role in burst promotion." |
| 4. |
Endothelin action on pituitary latotrophs (Bertram et al. 2006)
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Endothelin (ET-1, -2, and -3 designate three genes which produce different endothelin isopeptides) is a prolactin inhibiting substance of hypothalmic origin. ET-1 binding is part of at least four G protein signaling pathways in lactotrophs. The sequence of events in these pathways following the presentation of nano- and pico-molar concentrations of ET-1 is modeled in the paper. |
| 5. |
Low dose of dopamine may stimulate prolactin secretion by increasing K currents (Tabak et al. 2006)
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".. We considered
the fast K+ currents flowing through large-conductance
BK channels and through A-type channels. We developed a
minimal lactotroph model to investigate the effects of these
two currents. Both IBK and IA could transform the electrical
pattern of activity from spiking to bursting, but through
distinct mechanisms. IBK always increased the intracellular
Ca2+ concentration, while IA could either increase or
decrease it. Thus, the stimulatory effects of DA could be
mediated by a fast K+ conductance which converts tonically
spiking cells to bursters. In addition, the study illustrates that
a heterogeneous distribution of fast K+ conductances could
cause heterogeneous lactotroph firing patterns." |
| 6. |
Mixed mode oscillations as a mechanism for pseudo-plateau bursting (Vo et al. 2010)
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"We combine bifurcation analysis with the theory of canard-induced mixed mode oscillations to investigate the dynamics of a novel form of bursting. This bursting oscillation, which arises from a model of the electrical activity of a pituitary cell, is characterized by small impulses or spikes riding on top of an elevated voltage plateau. ..." |
| 7. |
Oxytocin and VIP involvement in prolactin secretion (Egli et al. 2004,2006, Bertram et al. 2006)
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"Prolactin (PRL) is secreted from lactotrophs of the anterior
pituitary gland of rats in a unique pattern in response to
uterine cervical stimulation (CS) during mating. Surges of
PRL secretion occur in response to relief from hypothalamic
dopaminergic inhibition and stimulation by hypothalamic releasing
neurohormones. In this study, we characterized the
role of oxytocin (OT) in this system and the involvement of
vasoactive intestinal polypeptide (VIP) from the suprachiasmatic
nucleus (SCN) in controlling OT and PRL secretion of
CS rats. ... OT
measurements of serial blood samples obtained from ovariectomized
(OVX) CS rats displayed a prominent increase at
the time of the afternoon PRL peak. The injection of VIP antisense
oligonucleotides into the SCN abolished the afternoon
increase of OT and PRL in CS-OVX animals. These findings
suggest that VIP from the SCN contributes to the regulation
of OT and PRL secretion in CS rats. We propose that in CS rats
the regulatory mechanism(s) for PRL secretion comprise coordinated
action of neuroendocrine dopaminergic and OT
cells, both governed by the daily rhythm of VIP-ergic output
from the SCN. This hypothesis is illustrated with a mathematical model." |
| 8. |
The dynamics underlying pseudo-plateau bursting in a pituitary cell model (Teka et al. 2011)
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" ... pseudo-plateau bursts, are unlike bursts studied mathematically in neurons (plateau bursting) and the standard fast-slow analysis used for plateau bursting is of limited use. Using an alternative fast-slow analysis, with one fast and two slow variables, we show that pseudo-plateau bursting is a canard-induced mixed mode oscillation. ..." See paper for other results. |
| 9. |
The relationship between two fast/slow analysis techniques for bursting oscill. (Teka et al. 2012)
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"Bursting oscillations in excitable systems reflect multi-timescale dynamics.
These oscillations have
often been studied in mathematical models by splitting the equations into fast and slow
subsystems.
Typically, one treats the slow variables as parameters of the fast subsystem and studies
the bifurcation structure of this subsystem.
This has key features such as a z-curve (stationary
branch) and a Hopf bifurcation that gives rise to a branch of periodic spiking solutions.
In models
of bursting in pituitary cells, we have recently used a different approach that focuses on the
dynamics of the slow subsystem.
Characteristic features of this approach are folded node
singularities and a critical manifold.
…
We find that the z-curve and Hopf bifurcation of the twofast/
one-slow decomposition are closely related to the voltage nullcline and folded node singularity
of the one-fast/two-slow decomposition, respectively. They become identical in the double singular
limit in which voltage is infinitely fast and calcium is infinitely slow."
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| 10. |
Understanding how fast activating K+ channels promote bursting in pituitary cells (Vo et al 2014)
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"...
Experimental
observations have shown ... that fast-activating
voltage- and calcium-dependent potassium (BK) current
tends to promote bursting in pituitary cells.
This burst promoting
effect requires fast activation of the BK current,
otherwise it is inhibitory to bursting. In this work, we analyze
a pituitary cell model in order to answer the question
of why the BK activation must be fast to promote bursting.
..." |
