Department of Neurobiology, Key Laboratory of Medical Neurobiology of Ministry of Health of China, Zhejiang Province Key Laboratory of Neurobiology, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310058, People's Republic of China.
J Membr Biol. 2013 Feb;246(2):101-7. doi: 10.1007/s00232-012-9506-7. Epub 2013 Jan 8.
Pancreatic beta cells act as glucose sensors, in which intracellular ATP (ATP) are altered with glucose concentration change. The characterization of voltage-gated sodium channels under different ATP remains unclear. Here, we demonstrated that increasing ATP within a certain range of concentrations (2-8 mM) significantly enhanced the voltage-gated sodium channel currents, compared with 2 mM cytosolic ATP. This enhancement was attenuated by even high intracellular ATP (12 mM). Furthermore, elevated ATP modulated the sodium channel kinetics in a dose-dependent manner. Increased ATP shifted both the current-voltage curve and the voltage-dependent inactivation curve of sodium channel to the right. Finally, the sodium channel recovery from inactivation was significantly faster when the intracellular ATP level was increased, especially in 8 mM ATP, which is an attainable concentration by the high glucose stimulation. In summary, our data suggested that elevated cytosolic ATP enhanced the activity of Na(+) channels, which may play essential roles in modulating β cell excitability and insulin release when blood glucose concentration increases.
胰岛β细胞作为葡萄糖感受器，其细胞内的 ATP(ATP))随着葡萄糖浓度的变化而改变。然而，在不同 ATP)水平下电压门控钠离子通道的特性仍不清楚。在这里，我们证明了在一定浓度范围内（2-8mM）增加 ATP)会显著增强电压门控钠离子通道电流，与 2mM 细胞质 ATP)相比。即使是高浓度的细胞内 ATP)(12mM)也会减弱这种增强作用。此外，升高的 ATP 以剂量依赖的方式调节钠通道动力学。增加 ATP)会使钠通道的电流-电压曲线和电压依赖性失活曲线同时右移。最后，当细胞内 ATP)水平升高时，钠通道从失活中恢复的速度明显加快，尤其是在 8mM ATP)时，这是高葡萄糖刺激下可达到的浓度。总之，我们的数据表明，升高的细胞质 ATP)增强了 Na(+)通道的活性，当血糖浓度升高时，这可能在调节β细胞兴奋性和胰岛素释放中发挥重要作用。
