- Author:
- Ethan Choi <mcho099@aucklanduni.ac.nz>
- Date:
- 2009-11-26 10:05:14+13:00
- Desc:
- Fixed equations using authors original code.
- Permanent Source URI:
- https://models.physiomeproject.org/workspace/tabak_toporikova_freeman_bertram_2007/rawfile/86ac1fa92c0bfb573e71a9afd251f5d6b5f59c99/tabak_toporikova_freeman_bertram_2007_a.cellml
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This CellML file was generated on 23/11/2009 at 4:22:19 at p.m. using:
COR (0.9.31.1333)
Copyright 2002-2009 Dr Alan Garny
http://cor.physiol.ox.ac.uk/ - cor@physiol.ox.ac.uk
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http://www.cellml.org/
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<title>Low dose of dopamine may stimulate prolactin secretion by increasing fast potassium currents</title>
<author>
<firstname>Catherine</firstname>
<surname>Lloyd</surname>
<affiliation>
<shortaffil>Bioengineering Institute, University of Auckland</shortaffil>
</affiliation>
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<section id="sec_status">
<title>Model Status</title>
<para>
The authors highlight that the original code they wrote for this model can be downloaded <ulink url="http://www.math.fsu.edu/~bertram/software/pituitary/JCNS_07.ode">here</ulink>. This particular CellML version of the model has the A-type potassium current switched off. For the alternative model which has the A-type current switched off and the BK-type potassium current switched on (gBK=0.2). This CellML model runs in PCEnv and COR to replicate the published results (figure 2B). Please note that the model needs to be run for at least 3000ms to allow the model to reach stability.
</para>
</section>
<sect1 id="sec_structure">
<title>Model Structure</title>
<para>
Prolactin (PRL) is a hormone which is synthesised and secreted by lactotrophs in the anterior lobe of the pituitary gland. It plays an important role in lactation, and influences many other physiological functions. Its release is inhibited by hypothalamic dopamine (DA), which acts through the D2 receptor to decrease PRL synthesis and secretion. The latter is decreased, at least in part, by hyperpolarisation of the lactotroph membrane, which prevents action potentials and the associated increase in intracellular calcium concentration that triggers PRL exocytosis. Membrane hyperpolarisation is caused by the activation of an inward rectifying potassium current, and an A-type potassium current is also increased by DA.
</para>
<para>
While this inhibitory effect occurs at DA concentrations between 0.1 and 10 micromolar, paradoxically, at much lower DA concentrations (less than 1 nanomolar) DA has a stimulatory effect on the release of PRL from lactotrophs. This stimulatory effect seems to be mediated, at least in part, through an increase in the intracellular calcium concentration. However, the definite biophysical mechanism underlying this phenomenon has not been identified.
</para>
<para>
In the paper described here, Tabak <emphasis>et al.</emphasis> investigate the idea that a calcium-activated fast potassium current (BK) might be responsible for the stimulatory effect of DA in lactotrophs. In addition, they explore the effects of DA on the fast, inactivating A-type potassium channel. To get a clearer understanding of the effects of DA on a lactotroph, they develop a mathematical model of the lactotroph. model simulations revealed the addition of either a BK-type current or an A-type current could transform a spontaneously spiking model to a bursting model, but the precise effect on the cytosolic calcium concentration was dependent on the type of current. Specifically, increasing the BK current increased the cytosolic calcium concentration, while increasing the A-type current could lead to either an increase or a decrease in cytosolic calcium depending on the model parameters.
</para>
<para>
The complete original paper reference is cited below:
</para>
<para>
Low dose of dopamine may stimulate prolactin secretion by increasing fast potassium currents, Joel Tabak, Natalia Toporikova, Marc E. Freeman, and Richard Bertram, 2007,
<emphasis>Journal of Computational Neuroscience</emphasis>
, 22, 211-222. <ulink url="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=AbstractPlus&list_uids=17058022&query_hl=1&itool=pubmed_docsum">PubMed ID: 17058022</ulink>
</para>
</sect1>
</article>
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<rdf:RDF xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#"><rdf:Description rdf:about="../../tabak/m"><title xmlns="http://purl.org/dc/elements/1.1/" xml:lang="en">m</title><alternative xmlns="http://purl.org/dc/terms/" xml:lang="en">voltage-dependent calcium current m gate</alternative></rdf:Description><rdf:Description rdf:about="../../tabak/I_Ca"><title xmlns="http://purl.org/dc/elements/1.1/" xml:lang="en">I_Ca</title><alternative xmlns="http://purl.org/dc/terms/" xml:lang="en">voltage-dependent calcium current</alternative></rdf:Description><rdf:Description rdf:about="../../tabak/Ca"><title xmlns="http://purl.org/dc/elements/1.1/" xml:lang="en">Ca</title><alternative xmlns="http://purl.org/dc/terms/" xml:lang="en">calcium</alternative></rdf:Description><rdf:Description rdf:about="rdf:#3de0a512-1c31-4ab7-b619-ea8c9f20e8dd"><Orgunit xmlns="http://www.w3.org/2001/vcard-rdf/3.0#" xml:lang="en">The Bioengineering Institute</Orgunit><Orgname 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Tabak, Toporikova, Freeman, and Bertram's 2007 mathematical model of a lactotroph, investigating how low doses of dopamine may stimulate prolactin secretion by increasing fast potassium currents.
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