Significance of Na/Ca Exchange for Ca²⁺ Buffering and Electrical Activity in Mouse Pancreatic β

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• 作者：David Gall ; Jesper Gromada ; Isabella Susa ; Patrik Rorsman ; André ; Herchuelz ; Krister Bokvist
• 刊名：Biophysical Journal
• 出版年：1999
• 出版时间：April 1999
• 年：1999
• 卷：76
• 期：4
• 页码：2018-2028
• 全文大小：181 K

文摘

We have combined the patch-clamp technique with microfluorimetry of the cytoplasmic Ca²⁺ concentration ([Ca²⁺]_i) to characterize Na/Ca exchange in mouse β-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 μM, 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 μM [Ca²⁺]_i) mechanism for Ca²⁺ removal. The β-cell Na/Ca exchanger is electrogenic and has a stoichiometry of three Na⁺ for one Ca²⁺. 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 [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 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.