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High external Ca2+ levels trigger membrane potential oscillations in mouse pancreatic beta-cells during blockade of
R M Santos1, R M Barbosa, A M Silva
1Center for Neurosciences of Coimbra, Department of Zoology, University of Coimbra, Portugal.
Abstract:
Glucose depolarizes the pancreatic beta-cell and induces membrane potential oscillations, but the nature of the underlying oscillatory conductance remains unknown. We have now investigated the effects of the Ca2+ ionophore ionomycin and high external Ca2+ concentration ([Ca2+]o) on glucose-induced electrical activity and whole islet intracellular free Ca2+ concentration ([Ca2+]i), under conditions where the K(ATP) channel was blocked (100 microM tolbutamide or 4 microM glibenclamide). Raising [Ca2+]o to 10.2 or 12.8 mM, but not to 5.1 or 7.7 mM, turned continuous electrical activity into bursting activity. High [Ca2+]o (12.8 mM) regenerated a pattern of fast [Ca2+]i oscillations overshooting the levels recorded in tolbutamide. Ionomycin (10 microM) raised the [Ca2+]i and synergized with 5.1 mM Ca2+ to hyperpolarize the beta-cell membrane. The data indicate that a [Ca2+]i-sensitive and sulphonylurea-insensitive oscillatory conductance underlies the beta-cell bursting activity.
Insights
Researchers identified a novel calcium-sensitive conductance in pancreatic beta-cells responsible for glucose-induced bursting activity, independent of ATP-sensitive potassium channels.
Area of Science:
- Endocrinology
- Cell Physiology
- Molecular Biology
Background:
- Glucose stimulates pancreatic beta-cells, causing electrical activity and oscillations.
- The specific ion channel responsible for glucose-induced beta-cell bursting remains unidentified.
Purpose of the Study:
- To investigate the role of extracellular calcium and ionomycin in glucose-induced electrical activity.
- To identify the oscillatory conductance underlying pancreatic beta-cell bursting.
Main Methods:
- Studied pancreatic beta-cell electrical activity and intracellular calcium ([Ca2+]i) in response to glucose.
- Utilized high extracellular calcium ([Ca2+]o) and the calcium ionophore ionomycin.
- Blocked ATP-sensitive potassium (K(ATP)) channels with tolbutamide or glibenclamide.
Main Results:
- Elevated [Ca2+]o (10.2-12.8 mM) induced bursting electrical activity from continuous activity.
- High [Ca2+]o (12.8 mM) caused rapid [Ca2+]i oscillations.
- Ionomycin increased [Ca2+]i and, with 5.1 mM Ca2+, hyperpolarized the beta-cell membrane.
Conclusions:
- A calcium ion concentration ([Ca2+]i)-sensitive conductance, insensitive to sulfonylureas, drives beta-cell bursting.
- This finding elucidates a key mechanism in glucose-stimulated insulin secretion.