BK Channels and the Control of the Pituitary

Abstract

The pituitary gland provides the important link between the nervous system and the endocrine system and regulates a diverse range of physiological functions. The pituitary is connected to the hypothalamus by the pituitary stalk and is comprised primarily of two lobes. The anterior lobe consists of five hormone-secreting cell types which are electrically excitable and display single-spike action potentials as well as complex bursting patterns. Bursting is of particular interest as it raises intracellular calcium to a greater extent than spiking and is believed to underlie secretagogue-induced hormone secretion. BK channels have been identified as a key regulator of bursting in anterior pituitary cells. Experimental data and mathematical modeling have demonstrated that BK activation during the upstroke of an action potential results in a prolonged depolarization and an increase in intracellular calcium. In contrast, the posterior lobe is primarily composed of axonal projections of magnocellular neurosecretory cells which extend from the supraoptic and paraventricular nuclei of the hypothalamus. In these neuroendocrine cells, BK channel activation results in a decrease in excitability and hormone secretion. The opposite effect of BK channels in the anterior and posterior pituitary highlights the diverse role of BK channels in regulating the activity of excitable cells. Further studies of pituitary cell excitability and the specific role of BK channels would lead to a greater understanding of how pituitary cell excitability is regulated by both hypothalamic secretagogues and negative feedback loops, and could ultimately lead to novel treatments to pituitary-related disorders.

Keywords: BK channels; Bursting; Corticotroph; Excitability; Modeling; Pituitary; Somatotroph.