Simulation of five intracellular Ca2+-regulation mechanisms in response to voltage-clamp pulses

González‐Vélez, Virginia; Godínez‐Fernández, J. Rafael

doi:10.1016/s0010-4825(03)00071-4

Cited by 11 publications

(11 citation statements)

References 11 publications

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Section: Methodsmentioning

confidence: 99%

“…Thus, considering that granule diameter is between 260 and 290 nm [19] and, that granules are located just below the plasma membrane [7] , we performed simulations to estimate local beneath the plasma membrane. We used our previously published model that estimates intracellular in concentric layers of specific thickness for a spherical cell considering buffered diffusion [29] ; to this model, we added a -extrusion pump [30] and a compensating leak flux. Leak flux was adjusted to obtain a steady-state close to 0.1 M. Assuming that an -cell could be approximated by a spherical cell of 5.3 m radius [19] with a large nucleus (60% of the cytoplasm), we obtained that to ratio ranges between 1.26 to 1.29 depending on the spatial extent considered for the layer beneath the membrane (from 10 to 300 nm).…”

Section: Methodsmentioning

confidence: 99%

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Model for Glucagon Secretion by Pancreatic α-Cells

et al. 2012

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Glucagon hormone is synthesized and released by pancreatic α-cells, one of the islet-cell types. This hormone, along with insulin, maintains blood glucose levels within the physiological range. Glucose stimulates glucagon release at low concentrations (hypoglycemia). However, the mechanisms involved in this secretion are still not completely clear. Here, using experimental calcium time series obtained in mouse pancreatic islets at low and high glucose conditions, we propose a glucagon secretion model for α-cells. Our model takes into account that the resupply of releasable granules is not only controlled by cytoplasmic , as in other neuroendocrine and endocrine cells, but also by the level of extracellular glucose. We found that, although calcium oscillations are highly variable, the average secretion rates predicted by the model fall into the range of values reported in the literature, for both stimulated and non-stimulated conditions. For low glucose levels, the model predicts that there would be a well-controlled number of releasable granules refilled slowly from a large reserve pool, probably to ensure a secretion rate that could last for several minutes. Studying the α-cell response to the addition of insulin at low glucose, we observe that the presence of insulin reduces glucagon release by decreasing the islet level. This observation is in line with previous work reporting that dynamics, mainly frequency, is altered by insulin [1]. Thus, the present results emphasize the main role played by and glucose in the control of glucagon secretion by α-cells. Our modeling approach also shows that calcium oscillations potentiate glucagon secretion as compared to constant levels of this cellular messenger. Altogether, the model sheds new light on the subcellular mechanisms involved in α-cell exocytosis, and provides a quantitative predictive tool for studying glucagon secretion modulators in physiological and pathological conditions.

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Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Model for Glucagon Secretion by Pancreatic α-Cells

et al. 2012

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“…Los modelos computacionales han sido ampliamente usados para simular la distribución espaciotemporal del Ca 2+ en el medio intracelular en diferentes tipos de células [183][184][185][186][187][188]. En estos modelos, tanto amortiguadores endógenos como exógenos han sido considerados ya que juegan un papel importante para la distribución del Ca 2+ intracelular.…”

Section: Modelos De La Difusión Amortiguada De Ca 2+unclassified

“…En estos modelos, tanto amortiguadores endógenos como exógenos han sido considerados ya que juegan un papel importante para la distribución del Ca 2+ intracelular. Diferentes métodos han sido empleados en estos estudios para resolver el problema de reacción-difusión resultante, estando entre estos los métodos de diferencias finitas [183][184][185]188], el método de Monte Carlo [186] y el método de los elementos finitos [187], que ha comenzado a usarse en este tipo de escenarios. Debido a las características y limitaciones de cada método, diferentes simplificaciones han sido consideradas.…”

Section: Modelos De La Difusión Amortiguada De Ca 2+unclassified

“…Debido a las características y limitaciones de cada método, diferentes simplificaciones han sido consideradas. Por ejemplo, los modelos basados en esquemas de diferencias finitas [183,184,188] asumen que los canales de Ca 2+ se encuentran uniformemente distribuidos en la membrana celular, despreciando aspectos geométricos importantes como la distribución no homogenea de los canales de Ca 2+ , los componentes tangenciales de la difusión y la curvatura de la célula. Por otro lado, el modelo de Gil et al [186], basado en el método de Monte Carlo, es capaz de considerar tanto la distribución y número de canales en una geometría tridimensional simplificada.…”

Section: Modelos De La Difusión Amortiguada De Ca 2+unclassified

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Modelo matemático de la actividad eléctrica y las oscilaciones de Ca2+ asociadas a la liberación de insulina en células ß humanas

Félix‐Martínez

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Exocytotic dynamics in human chromaffin cells: experiments and modeling

et al. 2012

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Chromaffin cells have been widely used to study neurosecretion since they exhibit similar calcium dependence of several exocytotic steps as synaptic terminals do, but having the enormous advantage of being neither as small or fast as neurons, nor as slow as endocrine cells. In the present study, secretion associated to experimental measurements of the exocytotic dynamics in human chromaffin cells of the adrenal gland was simulated by using a model that combines stochastic and deterministic approaches for short and longer depolarizing pulses, respectively. Experimental data were recorded from human chromaffin cells, obtained from healthy organ donors, using the perforated patch configuration of the patch-clamp technique. We have found that in human chromaffin cells, secretion would be mainly managed by small pools of non-equally fusion competent vesicles, slowly refilled over time. Fast secretion evoked by brief pulses can be predicted only when 75% of one of these pools (the "ready releasable pool" of vesicles, abbreviated as RRP) are co-localized to Ca²⁺ channels, indicating an immediately releasable pool in the range reported for isolated cells of bovine and rat (Álvarez and Marengo, J Neurochem 116:155-163, 2011). The need for spatial correlation and close proximity of vesicles to Ca²⁺ channels suggests that in human chromaffin cells there is a tight control of those releasable vesicles available for fast secretion.

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Simulation of five intracellular Ca2+-regulation mechanisms in response to voltage-clamp pulses

Cited by 11 publications

References 11 publications

Model for Glucagon Secretion by Pancreatic α-Cells

Model for Glucagon Secretion by Pancreatic α-Cells

Modelo matemático de la actividad eléctrica y las oscilaciones de Ca2+ asociadas a la liberación de insulina en células ß humanas

Exocytotic dynamics in human chromaffin cells: experiments and modeling

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