Evidence That Calcium Release-activated Current Mediates the Biphasic Electrical Activity of Mouse Pancreatic β-Cells
| Autor: | Illani Atwater, Arthur Sherman, N. F. Sheppard, Richard Bertram, Eduardo Rojas, D. Mears |
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| Rok vydání: | 1997 |
| Předmět: |
medicine.medical_specialty
Physiology Biophysics chemistry.chemical_element Biology Calcium Models Biological Calcium in biology Membrane Potentials Islets of Langerhans Mice Internal medicine medicine Diazoxide Animals Cells Cultured Membrane potential Voltage-dependent calcium channel T-type calcium channel Depolarization Cell Biology Hyperpolarization (biology) Glucose Endocrinology chemistry Female Calcium Channels medicine.drug |
| Zdroj: | Journal of Membrane Biology. 155:47-59 |
| ISSN: | 1432-1424 0022-2631 |
| DOI: | 10.1007/s002329900157 |
| Popis: | The electrical response of pancreatic β-cells to step increases in glucose concentration is biphasic, consisting of a prolonged depolarization with action potentials (Phase 1) followed by membrane potential oscillations known as bursts. We have proposed that the Phase 1 response results from the combined depolarizing influences of potassium channel closure and an inward, nonselective cation current (I CRAN) that activates as intracellular calcium stores empty during exposure to basal glucose (Bertram et al., 1995). The stores refill during Phase 1, deactivating I CRAN and allowing steady-state bursting to commence. We support this hypothesis with additional simulations and experimental results indicating that Phase 1 duration is sensitive to the filling state of intracellular calcium stores. First, the duration of the Phase 1 transient increases with duration of prior exposure to basal (2.8 mm) glucose, reflecting the increased time required to fill calcium stores that have been emptying for longer periods. Second, Phase 1 duration is reduced when islets are exposed to elevated K+ to refill calcium stores in the presence of basal glucose. Third, when extracellular calcium is removed during the basal glucose exposure to reduce calcium influx into the stores, Phase 1 duration increases. Finally, no Phase 1 is observed following hyperpolarization of the β-cell membrane with diazoxide in the continued presence of 11 mm glucose, a condition in which intracellular calcium stores remain full. Application of carbachol to empty calcium stores during basal glucose exposure did not increase Phase 1 duration as the model predicts. Despite this discrepancy, the good agreement between most of the experimental results and the model predictions provides evidence that a calcium release-activated current mediates the Phase 1 electrical response of the pancreatic β-cell. |
| Databáze: | OpenAIRE |
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