The role of Ca2+ feedback in shaping InsP3-evoked Ca2+ signals in mouse pancreatic acinar cells
The role of Ca2+ feedback in shaping InsP3-evoked Ca2+ signals in mouse pancreatic acinar cells
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DOI：
10.1111/j.1469-7793.1999.00187.x
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发表时间：
1999-10-01
影响因子：
5.5
通讯作者：
Thorn, P
中科院分区：
文献类型：
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作者：
Kidd, JF;Fogarty, KE;Thorn, P
1.细胞内Ca ~（2+）被认为是三磷酸肌醇（InsP（3））受体的正反馈和负反馈信号。然而，目前尚不清楚这可能如何影响体内的Ca 2+反应。采用膜片钳全细胞技术记录小鼠胰腺腺泡细胞内Ca 2+依赖性氯离子（Cl-（Ca））电流峰，并对注射Ins（2，4，5）P-3引起的胞浆Ca 2+峰进行成像。增加浓度的Ca 2+缓冲液（高达200 μ M EGTA或BAPTA）与当前激活阶段的步骤的外观和较小幅度的Cl-（Ca）尖峰的患病率。成像实验表明，随着缓冲液浓度的增加，分泌极胞浆内Ca 2+信号变得碎片化，空间离散的Ca 2+释放事件被消除.在较高的缓冲液浓度（200-500 μ M），增加浓度的EGTA增加尖峰频率和减少尖峰振幅。相反，BAPTA降低了锋电位频率，并维持了较大的锋电位振幅.我们的结论是，在InsP（3）诱发的尖峰，长距离的Ca 2+反馈（类似于2-4 μ m）形状的Ca 2+信号的上升阶段，通过协调离散的Ca 2+释放事件和短距离（类似于40 nm）的Ca 2+反馈的作用，以抑制进一步的Ca 2+释放。
1. Cytosolic Ca2+ has been proposed to act as both a positive and a negative feedback signal on the inositol trisphosphate (InsP(3)) receptor. However, it is unclear how this might affect the Ca2+ response in vivo.2. Mouse pancreatic acinar cells were whole-cell patch clamped to record the Ca2+-dependent chloride (Cl-(Ca)) current spikes and imaged to record the cytosolic Ca2+ spikes elicited by the injection of Ins(2,4,5)P-3. Increasing concentrations of Ca2+ buffer (up to 200 mu M EGTA or BAPTA) were associated with the appearance of steps in the current activation phase and a prevalence of smaller-amplitude Cl-(Ca) spikes. Imaging experiments showed that with increased buffer the secretory pole cytosolic Ca2+ signal became fragmented and spatially discrete Ca2+ release events were observed.3. At higher buffer concentrations (200-500 mu M), increasing concentrations of EGTA increased spike frequency and reduced spike amplitude. In contrast, BAPTA decreased spike frequency and maintained large spike amplitudes.4. We conclude that, during InsP(3)-evoked spiking, long-range Ca2+ feedback (similar to 2-4 mu m) shapes the rising phase of the Ca2+ signal by acting to co-ordinate discrete Ca2+ release events and short-range (similar to 40 nm) Ca2+ feedback acts to inhibit further Ca2+ release.