科研之友
微信
新浪微博
Facebook
分享链接
摘要
Whole-cell, patch-clamp recordings were carried out in acutely dissociated neurons from entorhinal cortex (EC) layer II to study the effects of Zn2+ on Na+ current kinetics and voltage dependence. In the presence of 200 mu M extracellular Cd2+ to abolish voltage-dependent Ca2+ currents, and 100 mM extracellular Na+, 1 mM Zn2+ inhibited the transient Na+ current, I-NaT, only to a modest degree (similar to 17% on average). A more pronounced inhibition (similar to 36%) was induced by Zn2+ when extracellular Na+ was lowered to 40 mM. Zn2+ also proved to modify I-NaT voltage-dependent and kinetic properties in multiple ways. Zn2+ (1 mM) shifted the voltage dependence of I-NaT activation and that of I-NaT onset speed in the positive direction by similar to 5 mV. The voltage dependence of I-NaT steady-state inactivation and that of I-NaT inactivation kinetics were markedly less affected by Zn2+. By contrast, I-NaT deactivation speed was prominently accelerated, and its voltage dependence was shifted by a significantly greater amount (similar to 8 mV on average) than that of I-NaT activation. In addition, the kinetics of I-NaT recovery from inactivation were significantly slowed by Zn2+. Zn2+ inhibition of I-NaT showed no signs of voltage dependence over the explored membrane-voltage window, indicating that the above effects cannot be explained by voltage dependence of Zn2+ induced channel-pore block. These findings suggest that the multiple, voltage-dependent state transitions that the Na+ channel undergoes through its activation path are differentially sensitive to the gating-modifying effects of Zn2+, thus resulting in differential modifications of the macroscopic current's activation, inactivation, and deactivation. Computer modeling provided support to this hypothesis.
- 出版日期2011-8
