ATP Regulates Sodium Channel Kinetics in Pancreatic Islet Beta Cells
ATP Regulates Sodium Channel Kinetics in Pancreatic Islet Beta Cells
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ATP 调节胰岛 β 细胞中的钠通道动力学
DOI：
10.1007/s00232-012-9506-7
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发表时间：
2013-02-01
影响因子：
2.4
通讯作者：
Shen, Ying
中科院分区：
文献类型：
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作者：
Zou, Na;Wu, Xiao;Shen, Ying
胰腺β细胞充当葡萄糖传感器，其中细胞内ATP（[ATP]（i））随葡萄糖浓度变化而改变。电压门控钠通道在不同[ATP]（i）下的特征仍不清楚。在这里，我们证明，与2 mM胞浆ATP相比，在一定浓度范围内（2-8 mM）增加[ATP]（i）显著增强电压门控钠通道电流。这种增强被甚至高的细胞内ATP（12 mM）减弱。此外，ATP升高以剂量依赖性方式调节钠通道动力学。增加[ATP]（i）使钠通道的电流-电压曲线和电压依赖性失活曲线右移。最后，当细胞内ATP水平增加时，钠通道从失活的恢复明显更快，特别是在8 mM [ATP]（i）中，这是高葡萄糖刺激可达到的浓度。总之，我们的数据表明，升高的胞浆ATP增强了Na+通道的活性，这可能在调节β细胞兴奋性和胰岛素释放时，血糖浓度增加发挥重要作用。
Pancreatic beta cells act as glucose sensors, in which intracellular ATP ([ATP](i)) are altered with glucose concentration change. The characterization of voltage-gated sodium channels under different [ATP](i) remains unclear. Here, we demonstrated that increasing [ATP](i) 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](i) 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](i), 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 beta cell excitability and insulin release when blood glucose concentration increases.