Significance of Na/Ca exchange for Ca21-buffering and electrical activity in mouse pancreatic b-cells. Biophys

ABSTRACT We have combined the patch-clamp technique with microfluorimetry of the cytoplasmic Ca21 concentration ([Ca21]i) to characterize Na/Ca exchange in mouse b-cells and to determine its importance for [Ca 21]i buffering and shaping of glucose-induced electrical activity. The exchanger contributes to Ca21 removal at [Ca21]i above 1 mM, where it accounts for.35 % of the total removal rate. At lower [Ca21]i, thapsigargin-sensitive Ca 21-ATPases constitute a major (70 % at 0.8 mM [Ca21]i) mechanism for Ca 21 removal. The b-cell Na/Ca exchanger is electrogenic and has a stoichiometry of three Na1 for one Ca21. The current arising from its operation reverses at;220 mV (current inward at more negative voltages), has a conductance of 53 pS/pF (14 mM [Ca21]i), and is abolished by removal of external Na 1 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 b-cells in intact islets and a slight (5 mV) hyperpolarization. Mathematical simulations suggest that the stimulatory action of glucose on b-cell electrical activity may be accounted for in part by glucose-induced reduction of the cytoplasmic Na1 concentration with resultant activation of the exchanger