Uptake and release of Ca2+ by the endoplasmic reticulum contribute to the oscillations of the cytosolic Ca2+ concentration triggered by Ca2+ influx in the electrically excitable pancreatic B-cell
Uptake and release of Ca2+ by the endoplasmic reticulum contribute to the oscillations of the cytosolic Ca2+ concentration triggered by Ca2+ influx in the electrically excitable pancreatic B-cell
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DOI：
10.1074/jbc.274.29.20197
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发表时间：
1999-07-16
影响因子：
4.8
通讯作者：
Henquin, JC
中科院分区：
文献类型：
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作者：
Gilon, P;Arredouani, A;Henquin, JC
在小鼠胰腺 B 细胞中研究了细胞内 Ca2+ 池在 Ca2+ 流入引发的胞质 Ca2+ 浓度 ([Ca2+](c)) 振荡中的作用。 [Ca2+](c) 振荡在葡萄糖刺激期间自发发生或由高 K+ 脉冲（在二氮嗪存在下）重复诱导，其特征在于两个组分的下降阶段。 [Ca2+](c) 的快速下降与电压依赖性 Ca2+ 通道的关闭同时发生，随后是与 Ca2+ 流入无关的较慢阶段。用毒胡萝卜素或环吡嗪酸阻断 SERCA 泵加速了 [Ca2+](c) 振荡的上升阶段并增加了其振幅，这表明内质网 (ER) 快速吸收 Ca2+。它还抑制了缓慢的 [Ca2+](c) 恢复阶段，这表明该阶段对应于在 [Ca2+](c) 瞬态上升期间被 ER 吸收的 Ca2+ 的缓慢释放。葡萄糖促进 ER 的缓冲能力并放大缓慢的 [Ca2+](c) 恢复阶段。高 KC 脉冲诱导的慢相不受 Ca2+- 调节剂或肌醇 1,4,5-三磷酸诱导的 Ca2+ 释放的影响，不涉及去极化诱导的 Ca2+ 释放，并且在笼中 Ca2+ 触发的 [Ca2+](c) 快速上升结束时也观察到。这是由于 Ca2+ 从 ER 被动泄漏所致。我们认为 ER 显示 Ca2+ 浓度 ([Ca2+](ER)) 的振荡与 [Ca2+](c) 相伴并平行。毒胡萝卜素使 B 细胞膜去极化的观察结果支持了内质网 Ca2+ 填充程度调节膜电位的观点。因此，葡萄糖刺激期间发生的[Ca2+](ER)振荡可能会影响B细胞的爆发行为，并最终影响[Ca2+](c)振荡。
The role of intracellular Ca2+ pools in oscillations of the cytosolic Ca2+ concentration ([Ca2+](c)) triggered by Ca2+ influx was investigated in mouse pancreatic B-cells. [Ca2+](c) oscillations occurring spontaneously during glucose stimulation or repetitively induced by pulses of high K+ (in the presence of diazoxide) were characterized by a descending phase in two components. A rapid decrease in [Ca2+](c) coincided with closure of voltage dependent Ca2+ channels and was followed by a slower phase independent of Ca2+ influx. Blocking the SERCA pump with thapsigargin or cyclopiazonic acid accelerated the rising phase of [Ca2+](c) oscillations and increased their amplitude, which suggests that the endoplasmic reticulum (ER) rapidly takes up Ca2+. It also suppressed the slow [Ca2+](c) recovery phase, which indicates that this phase corresponds to the slow release of Ca2+ that was taken up by the ER during the upstroke of the [Ca2+](c) transient. Glucose promoted the buffering capacity of the ER and amplified the slow [Ca2+](c) recovery phase. The slow phase induced by high KC pulses was not affected by modulators of Ca2+- or inositol 1,4,5-trisphosphate-induced Ca2+ release, did not involve a depolarization-induced Ca2+ release, and was also observed at the end of a rapid rise in [Ca2+](c) triggered from caged Ca2+. It is attributed to passive leakage of Ca2+ from the ER, We suggest that the ER displays oscillations of the Ca2+ concentration ([Ca2+](ER)) concomitant and parallel to [Ca2+](c). The observation that thapsigargin depolarizes the membrane of B-cells supports the proposal that the degree of Ca2+ filling of the ER modulates the membrane potential. Therefore, [Ca2+](ER) oscillations occurring during glucose stimulation are likely to influence the bursting behavior of B-cells and eventually [Ca2+](c) oscillations.