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We have combined the patch-clamp technique with microfluorimetry of the cytoplasmic Ca2+ concentration ([Ca2+]i) to characterize Na/Ca exchange in mouse beta-cells and to determine its importance for [Ca2+]i buffering and shaping of glucose-induced electrical activity. The exchanger contributes to Ca2+ removal at [Ca2+]i above 1 microM, where it accounts for >35% of the total removal rate. At lower [Ca2+]i, thapsigargin-sensitive Ca2+-ATPases constitute a major (70% at 0.8 microM [Ca2+]i) mechanism for Ca2+ removal. The beta-cell Na/Ca exchanger is electrogenic and has a stoichiometry of three Na+ for one Ca2+. The current arising from its operation reverses at approximately -20 mV (current inward at more negative voltages), has a conductance of 53 pS/pF (14 microM [Ca2+]i), and is abolished by removal of external Na+ or by intracellularly applied XIP (exchange inhibitory peptide). Inhibition of the exchanger results in shortening (50%) of the bursts of action potentials of glucose-stimulated beta-cells in intact islets and a slight (5 mV) hyperpolarization. Mathematical simulations suggest that the stimulatory action of glucose on beta-cell electrical activity may be accounted for in part by glucose-induced reduction of the cytoplasmic Na+ concentration with resultant activation of the exchanger.

Original publication

DOI

10.1016/S0006-3495(99)77359-5

Type

Journal article

Journal

Biophys J

Publication Date

04/1999

Volume

76

Pages

2018 - 2028

Keywords

Action Potentials, Adenosine Triphosphate, Animals, Biophysical Phenomena, Biophysics, Buffers, Calcium, Calcium-Transporting ATPases, Enzyme Inhibitors, Fluorometry, In Vitro Techniques, Ion Transport, Islets of Langerhans, Membrane Potentials, Mice, Models, Biological, Patch-Clamp Techniques, Sodium, Sodium-Calcium Exchanger, Thapsigargin