Gall D, Gromada J, Susa I, Rorsman P, Herchuelz A, Bokvist K
Laboratoire de Pharmacodynamie et de Thérapeutique, Faculté de Médecine, Université Libre de Bruxelles, B-1070 Bruxelles, Belgium.
Biophys J. 1999 Apr;76(4):2018-28. doi: 10.1016/S0006-3495(99)77359-5.
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.
我们将膜片钳技术与细胞质钙离子浓度（[Ca2+]i）的微量荧光测定法相结合，以表征小鼠β细胞中的钠钙交换，并确定其对[Ca2+]i缓冲以及葡萄糖诱导的电活动形成的重要性。在[Ca2+]i高于1微摩尔时，该交换器有助于钙离子的清除，其清除率占总清除率的35%以上。在较低的[Ca2+]i时，毒胡萝卜素敏感的钙离子ATP酶是钙离子清除的主要机制（在[Ca2+]i为0.8微摩尔时占70%）。β细胞钠钙交换器是生电性的，其化学计量比为三个钠离子交换一个钙离子。其运作产生的电流在约-20毫伏时反转（在更负的电压下电流向内），在14微摩尔[Ca2+]i时电导为53皮安/皮法，通过去除细胞外钠离子或细胞内应用XIP（交换抑制肽）可消除该电流。抑制该交换器会导致完整胰岛中葡萄糖刺激的β细胞动作电位爆发缩短（50%）以及轻微超极化（5毫伏）。数学模拟表明，葡萄糖对β细胞电活动的刺激作用可能部分归因于葡萄糖诱导的细胞质钠离子浓度降低，从而激活了该交换器。
