TRPM4通道抑制剂9-菲酚对胰岛β细胞INS-1电活动的抑制作用

Inhibitory effects of a TRPM4 inhibitor 9-phenanthrol on electrical activity of INS-1 pancreaticβ-cells

细胞内钙激活通透单价阳离子的瞬时受体电位M4(transient receptor potential melastatin 4,TRPM4)通道在胰岛β细胞表达,但是调节TRPM4的功能是否影响胰岛细胞的电活动尚需研究。本研究通过电生理方法,探讨了TRPM4通道抑制剂9-菲酚对胰岛β细胞动作电位发放的影响。采用全细胞电流钳技术,记录了不同浓度9-菲酚对胰岛β细胞放电频率、电位峰值及振幅的影响。结果显示,9-菲酚对甲苯磺丁脲刺激胰岛β细胞产生的动作电位发放频率有显著的抑制作用,且呈剂量依赖性,IC_(50)值为14.99±7.93μmol·L^(-1)。此外,9-菲酚对电刺激胰岛β细胞产生的动作电位发放频率也有相似的剂量依赖性抑制作用;对甲苯磺丁脲刺激胰岛β细胞产生的动作电位峰值和振幅也均有显著的抑制作用。本研究结果表明,TRPM4通道的功能能够影响胰岛β细胞动作电位的放电模式,为TRPM4通道在胰岛β细胞的研究提供了药理学实验方法和理论依据。

The Ca^(2+)-activated monovalent cation selective transient receptor potential melastatin 4(TRPM4)channel expressed in pancreaticβ-cells is implicated in theβ-cell function and insulin secretion,but how pharmacological function of TRPM4 channel affects membrane excitability ofβ-cells remains largely unknown.Here,we report that pharmacological inhibition of TRPM4 by specific inhibitor 9-phenanthrol attenuates electrical activities of pancreaticβ-cells.In whole-cell current clamp recordings,9-phenanthrol results in inhibition of action potential frequency induced by tolbutamide of the INS-1 pancreaticβ-cells in a dose-dependent manner with an IC_(50)value of 14.99±7.93μmol·L^(-1).Similarly,9-phenanthrol also inhibited action potential firing in INS-1 cells stimulated by current injection.Further recordings ofβ-cells demonstrate the significant inhibitory effects on action potential peak and action potential amplitude by 9-phenanthrol.Taken together,our results show the involvement of TRPM4 channel function in pancreaticβ-cells depolarization and action potential,it provides pharmacological experimental methods and theoretical support for the study of TRPM4 channel in pancreaticβ-cells.