Abstract
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.
Highlights
The crucial role of noise in many biological systems has only recently started to be fully appreciated [1]
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
We determine what causes the different types of electrical activity seen in pituitary cells
Summary
The crucial role of noise in many biological systems has only recently started to be fully appreciated [1]. Noise can even be beneficial to biological systems, leading, for example, to quicker evolution in changing environments and improved signal detection [4, 5]. For electrically excitable cells, such as neurons, a major source of noise comes from stochastic ion channel kinetics [6]. We study the effect of realistic ion channel noise in endocrine cells within the anterior pituitary. For these cells, the rate of hormone release is influenced by the pattern of membrane electrical activity, which in turn is controlled by the stochastic opening and closing of membrane ion channels. Gonadotroph cells produce spontaneous sharp action potentials (spikes) that cause little hormone secretion, whereas somatotrophs and lactotrophs exhibit spontaneous bursts in electrical activity that are sufficiently prolonged to elevate the intracellular calcium concentration and stimulate substantial hormone secretion [7]
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