<?xml version="1.0"?>
<!-- FILE : tabak_model_2007.xml
CREATED : 7th August 2007
LAST MODIFIED : 26th November 2009
AUTHOR : Catherine Lloyd
Bioengineering Institute
The University of Auckland
MODEL STATUS : This model conforms to the CellML 1.1 Specification.
DESCRIPTION : This file contains a CellML description of 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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<documentation xmlns="http://cellml.org/tmp-documentation">
<article>
<articleinfo>
<title>Low dose of dopamine may stimulate prolactin secretion by increasing fast potassium currents</title>
<author>
<firstname>Catherine</firstname>
<surname>Lloyd</surname>
<affiliation>
<shortaffil>Auckland Bioengineering Institute, The University of Auckland</shortaffil>
</affiliation>
</author>
</articleinfo>
<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 on (gA=25). For the alternative model which has the BK-type current switched on and the A-type potassium current switched off please see the gBK version of the model. This CellML model runs in PCEnv and COR to replicate the published results (figure 5c). 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>
ABSTRACT: Dopamine (DA) released from the hypothalamus tonically inhibits pituitary lactotrophs. DA (at micromolar concentration) opens potassium channels, hyperpolarizing the lactotrophs and thus preventing the calcium influx that triggers prolactin hormone release. Surprisingly, at concentrations ~1000 lower, DA can stimulate prolactin secretion. Here, we investigated whether an increase in a K+ current could mediate this stimulatory effect. 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 I BK and I A could transform the electrical pattern of activity from spiking to bursting, but through distinct mechanisms. I BK always increased the intracellular Ca2+ concentration, while I A 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.
</para>
<informalfigure float="0" id="fig_reaction_diagram">
<mediaobject>
<imageobject>
<objectinfo>
<title>model diagram</title>
</objectinfo>
<imagedata fileref="tabak_2007.png"/>
</imageobject>
</mediaobject>
<caption>Schematic diagram of the model.</caption>
</informalfigure>
<para>
The 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>
</documentation>
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Low dose of dopamine may stimulate prolactin secretion by increasing fast potassium currents (A-Type K Current)
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