Is Bursting More Effective than Spiking in Evoking Pituitary Hormone Secretion? A Spatiotemporal Simulation Study of Calcium and Granule Dynamics
Alessia Tagliavini, Joel Tabak, Richard Bertram, Morten Gram Pedersen
Endocrine cells of the pituitary gland secrete a number of hormones, and the amount of hormone released by a cell is controlled in large part by the cell's electrical activity and subsequent calcium influx. Typical electrical behaviors of pituitary cells include continuous spiking and so-called pseudo-plateau bursting. It has been shown that the amplitude of calcium fluctuations is greater in bursting cells, leading to the hypothesis that bursting cells release more hormone than spiking cells. In this work, we apply computer simulations to test this hypothesis. We use experimental recordings of electrical activity as input to mathematical models of calcium channel activity, buffered calcium diffusion, and calcium-driven exocytosis. To compare the efficacy of spiking and bursting on the same cell, we pharmacologically block the large conductance potassium (BK) current from a bursting cell, or add a BK current to a spiking cell via dynamic clamp. We find that bursting is generally at least as effective as spiking at evoking hormone release, and is often considerably more effective, even when normalizing to calcium influx. Our hybrid experimental/modeling approach confirms that adding a BK-type potassium current, which is typically associated with decreased cell activity and reduced secretion, can actually produce an increase in hormone secretion, as suggested earlier.