Abstract
We have combined the patch-clamp technique with microfluorimetry of the cytoplasmic Ca 2+ concentration ([Ca 2+] i) to characterize Na/Ca exchange in mouse β-cells and to determine its importance for [Ca 2+] i buffering and shaping of glucose-induced electrical activity. The exchanger contributes to Ca 2+ removal at [Ca 2+] i above 1 μM, where it accounts for >35% of the total removal rate. At lower [Ca 2+] i, thapsigargin-sensitive Ca 2+-ATPases constitute a major (70% at 0.8 μM [Ca 2+] i) mechanism for Ca 2+ removal. The β-cell Na/Ca exchanger is electrogenic and has a stoichiometry of three Na + for one Ca 2+. The current arising from its operation reverses at ∼−20 mV (current inward at more negative voltages), has a conductance of 53 pS/pF (14 μM [Ca 2+] 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 β-cells in intact islets and a slight (5 mV) hyperpolarization. Mathematical simulations suggest that the stimulatory action of glucose on β-cell electrical activity may be accounted for in part by glucose-induced reduction of the cytoplasmic Na + concentration with resultant activation of the exchanger.
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