TRPM4 impacts on Ca2+ signals during agonist-induced insulin secretion in pancreatic β-cells
TRPM4 impacts on Ca2+ signals during agonist-induced insulin secretion in pancreatic β-cells
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DOI：
10.1016/j.mce.2008.11.011
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发表时间：
2009-02-27
影响因子：
4.1
通讯作者：
Cheng, H.
中科院分区：
文献类型：
--
作者：
Marigo, V.;Courville, K.;Cheng, H.
TRPM4是一种钙激活的非选择性阳离子通道，参与细胞去极化，对胰岛β细胞内钙内流和胰岛素分泌具有重要作用。我们研究了TRPM4在P细胞系HIT-T15(仓鼠)、RINm5F(大鼠)、β-TC3(小鼠)、Min-6(小鼠)和α细胞系INR1G9(仓鼠)中的表达和功能。通过RT-PCR，我们鉴定了TRPM4在α细胞和β细胞中的转录本。在膜片钳记录中，随着钙离子浓度的增加，TRPM4的激活呈剂量依赖性，从仓鼠来源的细胞中记录到的去极化电流最大。此外，钙成像实验显示，与对照细胞相比，显性-负性效应对TRPM4的抑制显著降低了激动剂刺激产生的钙信号的幅度。[Ca~(2+)]降低，导致胰岛素分泌减少。我们的数据表明，TRPM4产生的去极化电流是控制细胞内钙信号的重要组成部分，这些信号是胰岛素分泌所必需的，也可能是阿尔法细胞分泌胰高血糖素所必需的。(C)2008爱思唯尔爱尔兰有限公司。版权所有。
TRPM4 is a Ca2+-activated non-selective cation (CAN) channel that functions in cell depolarization, which is important for Ca2+ influx and insulin secretion in pancreatic beta-cells. We investigated TRPM4 expression and function in the P-cell lines HIT-T15 (hamster), RINm5F (rat), beta-TC3 (mouse), MIN-6 (mouse) and the alpha-cell line INR1G9 (hamster). By RT-PCR, we identified TRPM4 transcripts in alpha- and beta-cells. Patch-clamp recordings with increasing Ca2+ concentrations resulted in a dose-dependent activation of TRPM4 with the greatest depolarizing currents recorded from hamster-derived cells. Further, Ca2+ imaging experiments revealed that inhibition of TRPM4 by a dominant-negative effect significantly decreased the magnitude of the Ca2+ signals generated by agonist stimulation compared to control cells. The decrease in the [Ca2+], resulted in reduced insulin secretion. Our data suggest that depolarizing currents generated by TRPM4 are an important component in the control of intracellular Ca2+ signals necessary for insulin secretion and perhaps glucagon from alpha-cells.(c) 2008 Elsevier Ireland Ltd. All rights reserved.