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Endoplasmic reticulum calcium store regulates membrane potential in mouse islet beta-cells
J F Worley1, M S McIntyre, B Spencer
1Department of Cell Physiology, Glaxo Research Institute, Research Triangle Park, North Carolina 27709.
The Journal of Biological Chemistry
|May 20, 1994
Summary
Glucose stimulates insulin secretion by depolarizing islet beta-cells, increasing intracellular calcium. A novel pathway activates an inward current when calcium stores are depleted, further enhancing insulin release.
Area of Science:
- * Cellular physiology
- * Endocrinology
- * Molecular biology
Background:
- * Glucose-stimulated insulin secretion (GSIS) is crucial for glucose homeostasis.
- * GSIS involves membrane depolarization and intracellular calcium ([Ca2+]i) elevation.
- * [Ca2+]i originates from both extracellular influx and intracellular stores.
Purpose of the Study:
- * To investigate a novel pathway linking intracellular calcium store depletion to beta-cell depolarization.
- * To elucidate the mechanism by which endoplasmic reticulum calcium store depletion influences beta-cell function.
Main Methods:
- * Experiments conducted on single islet beta-cells.
- * Utilized thapsigargin to prevent calcium store refilling.
- * Employed external EGTA to deplete intracellular calcium stores and measured associated currents.
Main Results:
- * Thapsigargin treatment caused sustained depolarization and enhanced calcium influx.
- * EGTA-induced calcium store depletion reduced [Ca2+]i and induced long-lasting depolarization.
- * EGTA activated a novel inward current distinct from voltage-dependent calcium channels.
Conclusions:
- * A novel pathway exists where depleted endoplasmic reticulum calcium stores activate an inward current.
- * This current induces depolarization, facilitating calcium influx via voltage-gated calcium channels.
- * This pathway plays a physiological role in controlling beta-cell function and insulin secretion.