Dominant role of sarcoendoplasmic reticulum Ca2+-ATPase pump in Ca2+ homeostasis and ecosytosis in rat pancreatic β-cells
Dominant role of sarcoendoplasmic reticulum Ca2+-ATPase pump in Ca2+ homeostasis and ecosytosis in rat pancreatic β-cells
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DOI：
10.1210/en.2005-1023
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发表时间：
2006-03-01
期刊：
影响因子：
4.8
通讯作者：
Tse, A
中科院分区：
文献类型：
--
作者：
Hughes, E;Lee, AK;Tse, A
胰岛素β细胞中含有胰岛素颗粒的胞吐作用受细胞质Ca2+浓度的变化（[Ca2+]（i））的变化严格调节。我们研究了Sarco-肾上腺胞浆Ca2+ATPase（SERCA）泵，Na+/ Ca2+交换器和质膜Ca2+ATPase Pump在单个大鼠胰腺β细胞的CA2+动力学中的作用。当膜电势被夹在-70 mV处（以3 mm葡萄糖为22或35 C）时，SERCA泵抑制作用急剧减慢（类似于4倍）胞质CA2+清除率，并导致基底[Ca2+]的持续增长（i）通过激活电容性Ca2+进入。 SERCA泵的抑制增加（类似于1.8倍），在大约22 C下触发的去极化触发的Ca2+瞬变幅度。抑制Na+/ Ca2+交换器或质膜CA2+ ATPase泵对CA2+动力学的效果较小。同时测量[Ca2+]（I）和胞吐作用（具有电容测量）表明，SERCA泵抑制增加了去极化触发的胞吐作用的幅度。胞吞作用的这种增强不是由于胞质Ca2+清除率的减慢，而是与去极化触发的Ca2+瞬态的峰值的增加密切相关。当在类似的[Ca2+]（i）与对照组中进行比较时，在SERCAPUMP抑制期间基底[Ca2+]（i）的上升并不会在随后的去极化触发的胞吐作用的大小上引起任何增强。因此，我们得出的结论是，在大鼠胰腺β细胞中，SERCA泵对Ca2+的快速吸收限制了去极化的峰幅度 - 触发的[Ca2+]（i）上升，从而控制了胰岛素分泌的量。
The exocytosis of insulin- containing granules from pancreatic beta- cells is tightly regulated by changes in cytosolic Ca2+ concentration ([ Ca2+] (i)). We investigated the role of the sarco-endoplasmic reticulum Ca2+- ATPase ( SERCA) pump, Na+/ Ca2+ exchanger, and plasma membrane Ca2+- ATPase pump in the Ca2+ dynamics of single rat pancreatic beta-cells. When the membrane potential was voltage clamped at - 70 mV ( in 3 mM glucose at similar to 22 or 35 C), SERCA pump inhibition dramatically slowed ( similar to 4- fold) cytosolic Ca2+ clearance and caused a sustained rise in basal [ Ca2+](i) via the activation of capacitative Ca2+ entry. SERCA pump inhibition increased ( similar to 1.8- fold) the amplitude of the depolarization- triggered Ca2+ transient at approximately 22 C. Inhibition of the Na+/ Ca2+ exchanger or plasma membrane Ca2+- ATPase pump had only minor effects on Ca2+ dynamics. Simultaneous measurement of [ Ca2+](i) and exocytosis ( with capacitance measurement) revealed that SERCA pump inhibition increased the magnitude of depolarization-triggered exocytosis. This enhancement in exocytosis was not due to the slowing of the cytosolic Ca2+ clearance but was closely correlated to the increase in the peak of the depolarization-triggered Ca2+ transient. When compared at similar [ Ca2+](i) with controls, the rise in basal [ Ca2+](i) during SERCApump inhibition did not cause any enhancement in the magnitude of the ensuing depolarization- triggered exocytosis. Therefore, we conclude that in rat pancreatic beta- cells, the rapid uptake of Ca2+ by SERCA pump limits the peak amplitude of depolarization- triggered [ Ca2+](i) rise and thus controls the amount of insulin secretion.