T-type calcium channels facilitate insulin secretion by enhancing general excitability in the insulin-secreting beta-cell line, INS-1
T-type calcium channels facilitate insulin secretion by enhancing general excitability in the insulin-secreting beta-cell line, INS-1
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DOI：
10.1210/en.138.9.3735
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发表时间：
1997-09-01
期刊：
影响因子：
4.8
通讯作者：
Li, M
中科院分区：
文献类型：
--
作者：
Bhattacharjee, A;Whitehurst, RM;Li, M
本研究探讨了T型电压门控钙通道在胰岛素分泌细胞中的功能。我们采用全细胞电压和电流记录、电容测量以及放射免疫分析（RIA）技术，来确定T型钙通道在大鼠胰岛素分泌细胞系INS - 1的电活动调节以及刺激 - 分泌偶联中的作用。通过在电流钳模式下采用双脉冲方案，我们发现T型钙通道的激活提供了一种低阈值去极化电位，它降低了动作电位起始的潜伏期，并且还增加了动作电位的频率，而这两种效应都可被氯化镍（NiCl₂，一种选择性T型钙通道阻滞剂）的施用所消除。此外，与低频刺激相比，高频刺激的应用导致膜电容（ΔCm）发生更大的变化，这表明胰岛素分泌增加。我们证明了在INS - 1中，葡萄糖刺激的胰岛素分泌可被NiCl₂呈剂量依赖性地降低。我们得出结论，T型钙通道通过增强这些细胞的总体兴奋性来促进胰岛素分泌。鉴于低血糖和高胰岛素血症的病理影响，T型钙通道可能是一个治疗靶点。
The present study addresses the function of T-type voltage-gated calcium channels in insulin-secreting cells. We used whole-cell voltage and current recordings, capacitance measurements, and RIA techniques to determine the contribution of T-type calcium channels in modulation of electrical activity and in stimulus-secretion coupling in a rat insulin secreting cell line, INS-1. By employing a double pulse protocol in the current-clamp mode, we found that activation of T-type calcium channels provided a low threshold depolarizing potential that decreased the latency of onset of action potentials and furthermore increased the frequency of action potentials, both of which are abolished by administration of nickel chloride (NiCl2), a selective T-type calcium channel blocker. Moreover application of high frequency stimulation, as compared with low frequency stimulation, caused a greater change in membrane capacitance (Delta Cm), suggesting higher insulin secretion. We demonstrated that glucose stimulated insulin secretion in INS-1 is reduced dose dependently by NiCl2. We conclude that T-type calcium channels facilitate insulin secretion by enhancing the general excitability of these cells. In light of the pathological effects of both hypo and hyperinsulinemia, the T-type calcium channel may be a therapeutic target.