Low dose of dopamine may stimulate prolactin secretion by increasing fast potassium currents

Model Structure

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.

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.

In the paper described here, Tabak et al. 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.

The complete original paper reference is cited below:

Low dose of dopamine may stimulate prolactin secretion by increasing fast potassium currents, Joel Tabak, Natalia Toporikova, Marc E. Freeman, and Richard Bertram, 2007, Journal of Computational Neuroscience , 22, 211-222. (Full text and PDF versions of the article are available to journal subscribers on the Journal of Computational Neuroscience website.) PubMed ID: 17058022

The authors highlight that the original code they wrote for this model can be downloaded here. 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) please see version 1 variant 1 of the model.