Ion channel noise shapes the electrical activity of endocrine cells.

Author summary The pituitary gland, situated just below the brain, is the body's master hormone gland. Hormones produced by the pituitary control many essential functions, including growth, reproduction, and our response to emotional and physical stress. The cells that produce these hormones generate electrical activity, exactly like neurons, and this electrical activity controls the amount of hormone that is released. Here, we use mathematics and computing to help understand the electrical activity of these cells. This allows us to perform manipulations that we cannot do experimentally. In particular, we analyse a type of mathematical model that, for the first time, takes into account the role that is played by random processes within pituitary cells. These random processes are particularly important for these types of cell. Using this approach, we determine what causes the different types of electrical activity seen in pituitary cells. A particularly exciting aspect of this work is that it allows us, for the first time, to find out how the electrical activity of big cells is different to that for small cells. Long term, the aim of this work is to understand better how drugs affect hormone production and so suggest ways to reduce their side effects. Endocrine cells in the pituitary gland typically display either spiking or bursting electrical activity, which is related to the level of hormone secretion. Recent work, which combines mathematical modelling with dynamic clamp experiments, suggests the difference is due to the presence or absence of a few large-conductance potassium channels. Since endocrine cells only contain a handful of these channels, it is likely that stochastic effects play an important role in the pattern of electrical activity. Here, for the first time, we explicitly determine the effect of such noise by studying a mathematical model that includes the realistic noisy opening and closing of ion channels. This allows us to investigate how noise affects the electrical activity, examine the origin of spiking and bursting, and determine which channel types are responsible for the greatest noise. Further, for the first time, we address the role of cell size in endocrine cell electrical activity, finding that larger cells typically display more bursting, while the smallest cells almost always only exhibit spiking behaviour.