Bursting and calcium oscillations in pancreatic β-cells: specific pacemakers for specific mechanisms

Fridlyand, Leonid E.; Tamarina, Natalia A.; Philipson, Louis H.

doi:10.1152/ajpendo.00177.2010

Cited by 75 publications

(90 citation statements)

References 152 publications

(166 reference statements)

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“…The slow pacemaker depolarization between two successive plateaus would result from the gradual restoration of [Ca 2+ ]i and ATP:ADP ratio until the SK and K ATP channels are closed again, the background depolarizing conductance becoming sufficiently large to trigger a new burst of action potentials (for a recent review see ref. 28). Our results suggest that TWIK1 may contribute to this depolarizing background conductance.…”

Section: Discussionmentioning

confidence: 99%

TWIK1, a unique background channel with variable ion selectivity

Chatelain

Bichet

Douguet

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

123

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TWIK1 belongs to the family of background K + channels with two pore domains. In native and transfected cells, TWIK1 is detected mainly in recycling endosomes. In principal cells in the kidney, TWIK1 gene inactivation leads to the loss of a nonselective cationic conductance, an unexpected effect that was attributed to adaptive regulation of other channels. Here, we show that TWIK1 ion selectivity is modulated by extracellular pH. Although TWIK1 is K + selective at neutral pH, it becomes permeable to Na + at the acidic pH found in endosomes. Selectivity recovery is slow after restoration of a neutral pH. Such hysteresis makes plausible a role of TWIK1 as a background channel in which selectivity and resulting inhibitory or excitatory influences on cell excitability rely on its recycling rate between internal acidic stores and the plasma membrane. TWIK1−/− pancreatic β cells are more polarized than control cells, confirming a depolarizing role of TWIK1 in kidney and pancreatic cells.T wo-pore-domain potassium (K 2P ) channels constitute a unique class of background channels comprising 15 members in humans. They share the same overall architecture with four membrane-spanning segments (M1-M4), two pore domains (P1 and P2), and a large extracellular M1P1 loop. Active as dimers, they produce almost time-and voltage-independent currents that oppose membrane depolarization and cell excitability. K 2P channels have been involved in physiological functions as diverse as cellvolume regulation, apoptosis, adrenal gland development and primary hyperaldosteronism, vasodilatation, neuronal excitability and altered motor performance, central O 2 chemoreception and breathing control, perception of pain, polyunsaturated fatty acidmediated neuroprotection, and mood control. They constitute a major target of volatile anesthetics (for recent and extensive reviews on K 2P channels see refs. 1-4).Among K 2P channels, TWIK1 (also termed "K2P1" or "KCNK1") is atypical. Originally cloned from a kidney cDNA library, TWIK1 is expressed at significant levels in other tissues including heart, brain, pancreas, lung, and placenta (5-7). Upon heterologous expression, it forms homodimers (8) that produce only modest currents in Xenopus oocytes and almost no currents in cultured mammalian cells. Another hallmark is the fast inactivation of the TWIK1 currents. Because of this inactivation, their steady-state current-voltage (I-V) relationships display inward rectification, unlike the other K 2P currents that produce outwardly rectifying I-V relationships in physiological K + conditions. No native currents with similar properties have yet been reported despite the broad distribution of TWIK1. Another puzzling observation is provided by gene inactivation of TWIK1 in the mouse: Rather than a decrease of K + conductance in TWIK1−/− kidney cells, a decrease of a nonselective cationic conductance was observed that was associated with an increase in the resting membrane potential (9). More recently, it has been suggested that TWIK1 is responsible for par...

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Section: Discussionmentioning

confidence: 99%

TWIK1, a unique background channel with variable ion selectivity

Chatelain

Bichet

Douguet

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

123

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“…The pulsatility of insulin secretion can thus be accounted for by the periodic activation of VACCs. However, one puzzling feature, at least to the author, is an apparent disconnect between the periodicity of insulin secretion from single islets, which at roughly 5 min is reported to be rather insensitive to glucose concentration (43,107,550), and that of bursting, the frequency of which can be glucose-dependent and continuous in the presence of very high glucose (47, 160,555). Burst termination has been ascribed to the activation of slow Ca 2ϩ -activated Ca 2ϩ channels as [Ca 2ϩ ] c accumulated during a burst (18,131,552).…”

Section: Oscillatory Parametersmentioning

confidence: 99%

The Pancreatic β-Cell: A Bioenergetic Perspective

Nicholls

2016

Physiological Reviews

123

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The pancreatic ␤-cell secretes insulin in response to elevated plasma glucose. This review applies an external bioenergetic critique to the central processes of glucose-stimulated insulin secretion, including glycolytic and mitochondrial metabolism, the cytosolic adenine nucleotide pool, and its interaction with plasma membrane ion channels. The control mechanisms responsible for the unique responsiveness of the cell to glucose availability are discussed from bioenergetic and metabolic control standpoints. The concept of coupling factor facilitation of secretion is critiqued, and an attempt is made to unravel the bioenergetic basis of the oscillatory mechanisms controlling secretion. The need to consider the physiological constraints operating in the intact cell is emphasized throughout. The aim is to provide a coherent pathway through an extensive, complex, and sometimes bewildering literature, particularly for those unfamiliar with the field.

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“…A part of these ODEs is two currents: the Ca 2+ current through the Ca 2+ channel and the K + current through the K + channel. This model is electrical in nature and is similar to a model for action potentials in a pancreatic beta cell (Atwater et al, 1983;Chay and Keizer, 1983;Bertram et al, 2000;Fridlyand et al, 2003Fridlyand et al, , 2009Fridlyand et al, , 2010Bertram and Sherman, 2004;Tsaneva-Atanasova et al, 2006). Additional ODEs can be added to this model to account for changes in buffers that bind to Ca 2+ , and this is described by the term R i , where i represents an individual buffer species.…”

Section: A Mathematical Model To Recapitulate Ca 2+ Oscillationsmentioning

confidence: 99%

Buffering Capacity Explains Signal Variation in Symbiotic Calcium Oscillations

et al. 2012

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Legumes form symbioses with rhizobial bacteria and arbuscular mycorrhizal fungi that aid plant nutrition. A critical component in the establishment of these symbioses is nuclear-localized calcium (Ca 2+ ) oscillations. Different components on the nuclear envelope have been identified as being required for the generation of the Ca 2+ oscillations. Among these an ion channel, Doesn't Make Infections1, is preferentially localized on the inner nuclear envelope and a Ca 2+ ATPase is localized on both the inner and outer nuclear envelopes. Doesn't Make Infections1 is conserved across plants and has a weak but broad similarity to bacterial potassium channels. A possible role for this cation channel could be hyperpolarization of the nuclear envelope to counterbalance the charge caused by the influx of Ca 2+ into the nucleus. Ca 2+ channels and Ca 2+ pumps are needed for the release and reuptake of Ca 2+ from the internal store, which is hypothesized to be the nuclear envelope lumen and endoplasmic reticulum, but the release mechanism of Ca 2+ remains to be identified and characterized. Here, we develop a mathematical model based on these components to describe the observed symbiotic Ca 2+ oscillations. This model can recapitulate Ca 2+ oscillations, and with the inclusion of Ca 2+ -binding proteins it offers a simple explanation for several previously unexplained phenomena. These include long periods of frequency variation, changes in spike shape, and the initiation and termination of oscillations. The model also predicts that an increase in buffering capacity in the nucleoplasm would cause a period of rapid oscillations. This phenomenon was observed experimentally by adding more of the inducing signal.

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Bursting and calcium oscillations in pancreatic β-cells: specific pacemakers for specific mechanisms

Cited by 75 publications

References 152 publications

TWIK1, a unique background channel with variable ion selectivity

TWIK1, a unique background channel with variable ion selectivity

The Pancreatic β-Cell: A Bioenergetic Perspective

Buffering Capacity Explains Signal Variation in Symbiotic Calcium Oscillations

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