Calcium-activated K+ channels of mouse beta-cells are controlled by both store and cytoplasmic Ca2+: experimental and theoretical studies.
Calcium-activated K+ channels of mouse beta-cells are controlled by both store and cytoplasmic Ca2+: experimental and theoretical studies.
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DOI：
10.1085/jgp.20028581
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发表时间：
2002-09
期刊：
影响因子：
--
通讯作者：
Satin LS
中科院分区：
文献类型：
--
作者：
Goforth PB;Bertram R;Khan FA;Zhang M;Sherman A;Satin LS
最近在小鼠胰腺β细胞中鉴定了响应于模拟胰岛爆发而缓慢激活的新型钙依赖性钾电流（Kslow）（Göpel，S.O.，T. Kanno，S.巴格湖作者：J. Renström，and P. Rorsman. 1999. 114：759-769）。Kslow激活可能有助于终止驱动β细胞中Ca 2+内流和胰岛素分泌的Ca 2+依赖性动作电位的周期性爆发。在这里，我们报告说，当[Ca 2 +]i的处理被破坏，通过阻断钙摄取到ER与两个独立的代理商报告，以阻止肌/内质网钙ATP酶（SERCA），毒胡萝卜素（1-5 μM）或胰岛素（200 nM），Kslow是短暂的增强，然后抑制。Kslow振幅也可以通过增加细胞外葡萄糖浓度从5到10 mM来抑制。SERCA阻断剂对Kslow的双相调制不能用最小的数学模型来解释，在该模型中，[Ca 2 +]i被分为两个隔室，细胞溶质和ER，并且Kslow激活反映了由突发协议诱导的细胞溶质钙的变化。然而，实验结果再现的模型中，Kslow激活介导的局部池的[Ca 2 +]在位于ER和质膜之间的子空间。在该模型中，子空间[Ca 2 +]遵循胞质[Ca 2 +]的变化，但具有反映来自ER的Ca 2+流出的梯度。当ER排空和填充时，缓慢调节该梯度可能增强Kslow和[Ca 2 +]处理在影响β细胞电活动和胰岛素分泌中的作用。
A novel calcium-dependent potassium current (Kslow) that slowly activates in response to a simulated islet burst was identified recently in mouse pancreatic β-cells (Göpel, S.O., T. Kanno, S. Barg, L. Eliasson, J. Galvanovskis, E. Renström, and P. Rorsman. 1999. J. Gen. Physiol. 114:759–769). Kslow activation may help terminate the cyclic bursts of Ca2+-dependent action potentials that drive Ca2+ influx and insulin secretion in β-cells. Here, we report that when [Ca2+]i handling was disrupted by blocking Ca2+ uptake into the ER with two separate agents reported to block the sarco/endoplasmic calcium ATPase (SERCA), thapsigargin (1–5 μM) or insulin (200 nM), Kslow was transiently potentiated and then inhibited. Kslow amplitude could also be inhibited by increasing extracellular glucose concentration from 5 to 10 mM. The biphasic modulation of Kslow by SERCA blockers could not be explained by a minimal mathematical model in which [Ca2+]i is divided between two compartments, the cytosol and the ER, and Kslow activation mirrors changes in cytosolic calcium induced by the burst protocol. However, the experimental findings were reproduced by a model in which Kslow activation is mediated by a localized pool of [Ca2+] in a subspace located between the ER and the plasma membrane. In this model, the subspace [Ca2+] follows changes in cytosolic [Ca2+] but with a gradient that reflects Ca2+ efflux from the ER. Slow modulation of this gradient as the ER empties and fills may enhance the role of Kslow and [Ca2+] handling in influencing β-cell electrical activity and insulin secretion.
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影响因子：
4.8
作者：
Gilon, P;Arredouani, A;Henquin, JC
通讯作者：
Henquin, JC
影响因子：
3.4
作者：
Bertram, R;Previte, J;Satin, LS
通讯作者：
Satin, LS
DOI：
10.1073/pnas.96.14.7650
发表时间：
1999-07-06
影响因子：
11.1
作者：
Cordoba-Rodriguez, R;Moore, KA;Weinreich, D
通讯作者：
Weinreich, D
DOI：
10.1152/ajpendo.00347.2001
发表时间：
2002-05-01
影响因子：
5.1
作者：
Arredouani, A;Henquin, JC;Gilon, P
通讯作者：
Gilon, P
影响因子：
4.1
作者：
Gromada, J;FrokjaerJensen, J;Dissing, S
通讯作者：
Dissing, S