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Journal ArticleDOI

Cell coupling in mouse pancreatic beta-cells measured in intact islets of Langerhans.

TLDR
Theoretical considerations indicate that the coupling between β-cells within the islet is sufficient to allow propagation of [Ca2+]i waves to spread with a speed of approximately 80 μm s−1, similar to that observed experimentally in confocal [Ca 2+] i imaging.
Abstract
The perforated whole-cell configuration of the patch-clamp technique was applied to functionally identified b-cells in intact mouse pancreatic islets to study the extent of cell coupling between adjacent b-cells. Using a combination of current- and voltage-clamp recordings, the total gap junctional conductance between b-cells in an islet was estimated to be 1.22 nS. The analysis of the current waveforms in a voltage-clamped cell (due to the firing of an action potential in a neighbouring cell) suggested that the gap junctional conductance between a pair of b-cells was 0.17 nS. Subthreshold voltage-clamp depolarization (to K55 mV) gave rise to a slow capacitive current indicative of coupling between b-cells, but not in non-b-cells, with a time constant of 13.5 ms and a total charge movement of 0.2 pC. Our data suggest that a superficial b-cell in an islet is in electrical contact with six to seven other b-cells. No evidence for dye coupling was obtained when cells were dialysed with Lucifer yellow even when electrical coupling was apparent. The correction of the measured resting conductance for the contribution of the gap junctional conductance indicated that the whole-cell KATP channel conductance (GK,ATP) falls from approximately 2.5 nS in the absence of glucose to 0.1 nS at 15 mM glucose with an estimated IC50 of approximately 4 mM. Theoretical considerations indicate that the coupling between b-cells within the islet is sufficient to allow propagation of [Ca 2C ]i waves to spread with a speed of approximately 80 m ms K1 , similar to that observed experimentally in confocal [Ca 2C ]i imaging.

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Citations
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Journal ArticleDOI

Pancreatic β-Cell Electrical Activity and Insulin Secretion: Of Mice and Men

TL;DR: Recent advances in understanding of the β-cell transcriptome, electrical activity, and insulin exocytosis are reviewed and models of how the different ion channels contribute to their electrical activity and insulin secretion are provided, and how these processes become perturbed in T2DM are discussed.
Journal ArticleDOI

Network science of biological systems at different scales: A review

TL;DR: This work presents research highlights ranging from determination of the molecular interaction network within a cell to studies of architectural and functional properties of brain networks and biological transportation networks, and focuses on synergies between network science and data analysis, which enable us to determine functional connectivity patterns in multicellular systems.
Journal ArticleDOI

Lipotoxicity disrupts incretin-regulated human β cell connectivity

TL;DR: It is demonstrated that β cell connectedness is an inherent property of human islets that is likely to influence incretin-potentiated insulin secretion and may be perturbed by diabetogenic insults to disrupt glucose homeostasis in humans.
Journal ArticleDOI

Regulation of calcium in pancreatic α- and β-cells in health and disease

TL;DR: The mechanisms that underlie the reciprocal regulation of insulin and glucagon secretion by changes in plasma glucose are discussed, the roles played by different types of voltage-gated Ca2+-channel present in α- and β-cells and the modulation of hormone secretion by Ca2-dependent and -independent processes are considered.
References
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Book

Ionic channels of excitable membranes

Bertil Hille
TL;DR: The Ionic Channel of Excitable Membranes (ICOMB) as discussed by the authors is an extended version of ICOMB with new chapters on fast chemical synapses, modulation through G protein coupled receptors and second messenger systems, molecules cloning, site directed mutagenesis, and cell biology.
Book

Ion Channels of Excitable Membranes

Bertil Hille
TL;DR: The superfamily of voltage-gated channels was studied in this paper, where a classical biophysics of the squid giant axon was discussed. But the superfamily was not considered in this paper.
Book ChapterDOI

Ion Channels in Excitable Membranes

TL;DR: The action potential is triggered when the membrane potential, which was at the resting level, depolarizes and reaches the threshold of excitation, which triggers the action potential.
Journal ArticleDOI

Structural and functional diversity of connexin genes in the mouse and human genome

TL;DR: This review compares currently identified connexin genes in both the mouse and human genome and discusses the functions of gap junctions deduced from targeted mouse mutants and human genetic disorders.
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