Low Dose of Dopamine may Stimulate Prolactin Secretion by Increasing Fast Potassium Currents

J. Tabak, N. Toporikova, M. E. Freeman, R. Bertram

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 potassium current could mediate this stimulatory effect. We considered the fast potassium 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 calcium concentration, while I_A could either increase or decrease it. Thus, the stimulatory effects of DA could be mediated by a fast potassium conductance which converts tonically spiking cells to bursters. In addition, the study illustrates that a heterogeneous distribution of fast potassium conductances could cause heterogeneous lactotroph firing patterns.