细胞外pH值对KCNQ2/3钾离子通道的调节

Modulation of KCNQ2 and KCNQ3 potassium channels by extracellular pH

目的 研究细胞外pH值改变对KCNQ2 /3钾离子通道的调节。方法 用体外转录法将KCNQ2 /3钾离子通道的mRNA,微注射于爪蟾卵母细胞中,表达KCNQ2 /3电流。用双电极电压钳方法 (TEVC)观察细胞外pH值对KCNQ2 /3通道的调节。结果 细胞外pH减小,抑制KCNQ2 /3电流,影响激活电压,而且这种调节有一定的电压和浓度依赖性。在阈电压附近 -60mV、pH 6 8时对KCNQ2 /3通道的影响最明显。pH值改变还会调节通道开放时程,影响通道激活时间常数。结论 在维持神经细胞静息电位、调节神经兴奋性方面起重要作用的KCNQ2 /3通道,受细胞外pH值调节,这种调节作用可能在神经细胞生理性兴奋和病理性变化中如:惊厥、癫痫、休克有重要意义。

Aim To study the modulation of KCNQ2/3 potassium cha nn els by extracellular pH.Methods In vitro transcription was used to synthesize cRNA of KCNQ2/3 potassium channels.The cRNA was injected into Xenopus oocytes to express the KCNQ2/3 channel.The modulation of KCNQ2/3 potass ium channels by extracellular pH was studied by two electrodes voltage clamp tec hniques.Results KCNQ2/3 currents were inhibited and current-vo ltage relationship of activation were shifted to the right with decreased extrac ellular pH. pH modulation of KCNQ2/3 currents was voltage dependent,with a more pronounced effect at more negative potentials above the activation threshold (-60 mV). Extracelluar pH also decreased activation and deactivation kinetics of KCNQ2/3 currents.Conclusion KCNQ2/3 channels, known to contr ibute to neuronal excitability, were modulated by extracelluar pH. The profound effects of the extracelluar pH exerted on KCNQ2/3 channel may play an important role during physiology neuronal activity and pathological events such a s epileptic seizures, cerebral ischemia and shock etc.