Flow and Voltage-dependence of Resurgent Na+ current in Subthalamic Neurons

• Main Authors: Sun-Li Chou, 周孫立
• Other Authors: 郭鐘金
• Format: Others
• Language: zh-TW
• Published: 2011
• Online Access: http://ndltd.ncl.edu.tw/handle/06215244770030982103

碩士 === 國立臺灣大學 === 生理學研究所 === 99 === Spontaneous firing in central nervous system plays an important role in epilepsy and idiopathic motor disorders. Subthalamic neurons show manifest resurgent Na+ currents. Previous studies suggest the possibility of voltage- and flow-dependence of sodium resurgent currents, but direct evidence is deficient. On the other hand, a hypothesis had been proposed that an endogenous protein may play a role in the generation of recurrent sodium currents. Although this hypothesis well explains well why inactivated channels reopens upon repolarization, some important molecular details remain to be characterized. In this study, step depolarization and steps repolarization to different voltage are designed to evoke transient sodium currents and resurgent sodium currents. We found incremental resurgent sodium currents following steps to more depolarized pre-pulse voltages between -20mV and +40mV. Voltage-dependence of the repolarizing pulse is also present between -50mV and -10mV. We also replaced part of the extracellular sodium chloride by cesium chloride to shift the reversal potential and thus changed the direction of either transient or resurgent sodium ion flow. Interestingly, outward transient sodium currents are followed by less noticeable resurgent sodium currents with the same voltage protocols if compared with inward transient sodium currents in the same neuron. However, the time to peak resurgent sodium currents is shorter when the preceding pulse elicits outward Na+ currents. The development of resurgent currents is also apparently “speeded” by outward transient sodium currents and outward resurgent sodium currents themselves. We conclude that the affinity between the endogenous protein and sodium channels may be modulated by both conformation changes of the channel and the direction of ionic flow through the pore.