Is bursting more effective than spiking in evoking pituitary hormone secretion? A spatiotemporal simulation study of calcium and granule dynamics

Tagliavini, Alessia; Tabak, Joël; Bertram, Richard; Pedersen, Morten Gram

doi:10.1152/ajpendo.00500.2015

Cited by 30 publications

(37 citation statements)

References 41 publications

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“…A relationship between cell size and tendency to burst has also been shown previously in a model of dopamine neurons, where dendrites and soma were increased by different factors to match the ratio of sizes between human and rat neurons [42]. Perhaps not surprisingly, this means that larger cells, with longer event durations, typically release more hormone than smaller cells [43].…”

Section: Discussionsupporting

confidence: 70%

Ion channel noise shapes the electrical activity of endocrine cells

2020

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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.

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Section: Discussionsupporting

confidence: 70%

Ion channel noise shapes the electrical activity of endocrine cells

2020

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“…The cells generate Ca 2+ -dependent action potentials, and a diverse family of Ca 2+ -activated K + channels regulate both electrical activity and activity-induced secretion from these cells [57,58]. Common electrical behaviors include continuous spiking and 'pseudo-plateau' bursting: the amplitude of fluctuations in intracellular Ca 2+ is greater in bursting cells, leading to the hypothesis that bursting cells release more hormone than spiking cells [59]. Gene transcription in endocrine cells also occurs in bursts or pulses of activity, and these seem to be linked to the bursts of electrical activity [60][61][62], raising the possibility that bursts of spikes are also more efficient in stimulating synthesis.…”

Section: The Anterior Pituitary Gland and The Hypothalamusmentioning

confidence: 99%

Models in neuroendocrinology

Leng

MacGregor

2018

Mathematical Biosciences

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The neuroendocrine systems of the hypothalamus are critical for survival and reproduction, and are highly conserved throughout vertebrate evolution. Their roles in controlling body metabolism, growth and body composition, stress, electrolyte balance and reproduction have been intensively studied, and have yielded a rich crop of original and challenging insights into neuronal function, insights that circumscribe a vision of the brain that is quite different from conventional views. Despite the diverse physiological roles of pituitary hormones, most are secreted in a pulsatile pattern, but arising through a variety of mechanisms. An important exception is vasopressin which uses bursting neural activity, but produces a graded secretion response to osmotic pressure, a sustained robust linear response constructed from noisy, nonlinear components. Neuroendocrine systems have many features such as multiple temporal scales and nonlinearity that make their underlying mechanisms hard to understand without mathematical modelling. The models presented here cover the wide range of temporal scales involved in these systems, including models of single cell electrical activity and calcium dynamics, receptor signalling, gene expression, coordinated activity of neuronal networks, whole-organism hormone dynamics and feedback loops, and the menstrual cycle. Many interesting theoretical approaches have been applied to these systems, but important problems remain, at the core the question of what is the true advantage of pulsatility.

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“…Recently, we exploited a hybrid experimental/modeling approach to explore the hypothesis that bursting cells release more hormone than spiking cells [67].…”

Section: How Do Different Pattern Of Electrical Activity Relate To Lomentioning

confidence: 99%

“…2). The shift from one type of electrical activity to the other was obtained using either BK channels blockers or the dynamic clamp technique, which injects an artificial BK-current into the cell [66,67].…”

Section: How Do Different Pattern Of Electrical Activity Relate To Lomentioning

confidence: 99%

“…This allowed us to calculate the average number of fused granules over time at different distances, and as a function of the total Ca 2+ charge entry. First, we assumed the presence of a primed pool of granules [67]. We observed that when the release site was located 100 nm from the channel, exocytosis would be similar with both spiking and bursting, since the Ca 2+ concentrations at the exocytotic machinery are in both cases saturating, and hence the primed pool is released at maximum speed within a few seconds whether driven by spiking or bursting electrical activity.…”

Section: How Do Different Pattern Of Electrical Activity Relate To Lomentioning

confidence: 99%

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Recent advances in mathematical modeling and statistical analysis of exocytosis in endocrine cells

Pedersen

Tagliavini

Cortese

et al. 2017

Mathematical Biosciences

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Most endocrine cells secrete hormones as a result of Ca-regulated exocytosis, i.e., fusion of the membranes of hormone-containing secretory granules with the cell membrane, which allows the hormone molecules to escape to the extracellular space. As in neurons, electrical activity and cell depolarization open voltage-sensitive Ca channels, and the resulting Ca influx elevate the intracellular Ca concentration, which in turn causes exocytosis. Whereas the main molecular components involved in exocytosis are increasingly well understood, quantitative understanding of the dynamical aspects of exocytosis is still lacking. Due to the nontrivial spatiotemporal Ca dynamics, which depends on the particular pattern of electrical activity as well as Ca channel kinetics, exocytosis is dependent on the spatial arrangement of Ca channels and secretory granules. For example, the creation of local Ca microdomains, where the Ca concentration reaches tens of µM, are believed to be important for triggering exocytosis. Spatiotemporal simulations of buffered Ca diffusion have provided important insight into the interplay between electrical activity, Ca channel kinetics, and the location of granules and Ca channels. By confronting simulations with statistical time-to-event (or survival) regression analysis of single granule exocytosis monitored with TIRF microscopy, a direct connection between location and rate of exocytosis can be obtained at the local, single-granule level. To get insight into whole-cell secretion, simplifications of the full spatiotemporal dynamics have shown to be highly helpful. Here, we provide an overview of recent approaches and results for quantitative analysis of Ca regulated exocytosis of hormone-containing granules.

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Is bursting more effective than spiking in evoking pituitary hormone secretion? A spatiotemporal simulation study of calcium and granule dynamics

Abstract: Tagliavini A, Tabak J, Bertram R, Pedersen MG. Is bursting more effective than spiking in evoking pituitary hormone secretion? A spatiotemporal simulation study of calcium and granule dynamics. Am

Cited by 30 publications

References 41 publications

Ion channel noise shapes the electrical activity of endocrine cells

Ion channel noise shapes the electrical activity of endocrine cells

Models in neuroendocrinology

Recent advances in mathematical modeling and statistical analysis of exocytosis in endocrine cells

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