Mathematical Biology Seminar

Joel Tabak
Department of Biological Science, Florida State university
Wednesday Jan. 16, 2008
3:05pm in LCB 215
"Fast potassium currents can stimulate calcium influx and hormone secretion in pituitary cells "

Abstract: Dopamine (DA) released from the hypothalamus tonically inhibits pituitary lactotrophs. DA opens potassium channels, hyperpolarizing the lactotrophs and thus preventing the calcium influx that triggers prolactin hormone release. Surprisingly, at concentrations ~1000 lower (sub nM), DA can increase intracellular calcium ([Ca++]i) and stimulate prolactin secretion. Can an increase in a K+ current mediate this stimulatory effect? To answer this question, we added either an inactivating (IA) or a non-inactivating (IBK) fast K+ current to a minimal lactotroph model. Both currents transformed the activity pattern of the model from spiking to bursting. This transition to bursting resulted in larger amplitude [Ca++]i oscillations. However, while IBK also caused a reliable increase in mean [Ca++]i, IA generally did not. The reason for this difference will be explained using fast/slow analysis. In the cases where IA did increase mean [Ca++]i, we observed that the bursting mechanism was no longer dependent on the slow variable [Ca++]i. Bursting could continue after [Ca++]i was clamped and therefore did not rely on the usual combination of bistability and a slow variable. The slow bursting time scale is unexpectedly caused by a transient pulse of IA at the beginning of each burst. We believe that this is the first example of a physiologically based, single-compartmental model of bursting with no slow subsystem.