Calcium Channels in Postnatal Development of Rat Pancreatic Beta Cells and Their Role in Insulin Secretion.
Calcium Channels in Postnatal Development of Rat Pancreatic Beta Cells and Their Role in Insulin Secretion.
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DOI：
10.3389/fendo.2018.00040
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发表时间：
2018
影响因子：
5.2
通讯作者：
Hiriart M
中科院分区：
文献类型：
--
作者：
García-Delgado N;Velasco M;Sánchez-Soto C;Díaz-García CM;Hiriart M
在发育的第一个月，胰岛β细胞获得功能成熟，使它们能够通过分泌胰岛素来应对细胞外葡萄糖浓度的变化。离子通道活性的变化对这种成熟很重要。在电压门控钙通道中，研究最多的是高电压激活的通道，主要是L型通道，而低电压激活的钙通道在天然β细胞中的研究较少。我们分析了VGCC在大鼠出生后β细胞发育过程中的表达和活性的变化。我们观察到，随着发育阶段的延长，T型电流的检出百分率逐渐增加。成体细胞的T型钙电流密度高于新生细胞和P20β细胞。平均HVA电流密度也随年龄增长而增加。P20β细胞的钙电流行为是不均匀的；几乎一半的细胞的HVA电流密度高于成年细胞，这与T型电流的存在无关。我们检测到各年龄段LVA通道的α1G、α1H和α1I亚单位的存在。CAV3.1亚基(α1G)表达最强。T型通道阻断剂米贝拉地尔和TTA-A2在5.6mM葡萄糖时显著抑制胰岛素的分泌，这表明在基础葡萄糖条件下T型通道具有生理作用。硝苯地平和TTA-A2都显著减少了在基础和刺激葡萄糖条件下分泌更多胰岛素的β细胞亚群。我们认为，VGCC在发育过程中的表达和活性的变化在β细胞的生理成熟过程中起着重要作用。
Pancreatic beta cells during the first month of development acquire functional maturity, allowing them to respond to variations in extracellular glucose concentration by secreting insulin. Changes in ionic channel activity are important for this maturation. Within the voltage-gated calcium channels (VGCC), the most studied channels are high-voltage-activated (HVA), principally L-type; while low-voltage-activated (LVA) channels have been poorly studied in native beta cells. We analyzed the changes in the expression and activity of VGCC during the postnatal development in rat beta cells. We observed that the percentage of detection of T-type current increased with the stage of development. T-type calcium current density in adult cells was higher than in neonatal and P20 beta cells. Mean HVA current density also increased with age. Calcium current behavior in P20 beta cells was heterogeneous; almost half of the cells had HVA current densities higher than the adult cells, and this was independent of the presence of T-type current. We detected the presence of α1G, α1H, and α1I subunits of LVA channels at all ages. The Cav 3.1 subunit (α1G) was the most expressed. T-type channel blockers mibefradil and TTA-A2 significantly inhibited insulin secretion at 5.6 mM glucose, which suggests a physiological role for T-type channels at basal glucose conditions. Both, nifedipine and TTA-A2, drastically decreased the beta-cell subpopulation that secretes more insulin, in both basal and stimulating glucose conditions. We conclude that changes in expression and activity of VGCC during the development play an important role in physiological maturation of beta cells.
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大鼠胰腺B细胞中的Na通道和两种类型的Ca通道用反向溶血斑块测定法鉴定出来。
DOI：
10.1085/jgp.91.5.617
发表时间：
1988-05
期刊：
The Journal of general physiology
影响因子：
--
作者：
Hiriart M;Matteson DR
通讯作者：
Matteson DR
影响因子：
4.6
作者：
Lombardi A;Gambardella J;Du XL;Sorriento D;Mauro M;Iaccarino G;Trimarco B;Santulli G
通讯作者：
Santulli G
影响因子：
3.4
作者：
Lee, JH;Gomora, JC;Perez-Reyes, E
通讯作者：
Perez-Reyes, E
DOI：
10.1152/ajpendo.00457.2006
发表时间：
2007-04-01
影响因子：
5.1
作者：
Navarro-Tableros, Victor;Fiordelisio, Tatiana;Hiriart, Marcia
通讯作者：
Hiriart, Marcia
影响因子：
4.8
作者：
Bhattacharjee, A;Whitehurst, RM;Li, M
通讯作者：
Li, M