Yan D, Wang L, Ma F-L, Deng H, Liu J, Li C, Wang H, Chen J, Tang J-L, Ruan D-Y
School of Life Science, University of Science and Technology of China, Hefei, Anhui, PR China.
Neuroscience. 2008 May 2;153(2):436-45. doi: 10.1016/j.neuroscience.2008.02.016. Epub 2008 Feb 20.
In this study, the effects of chronic lead (Pb(2+)) exposure, during day 0 of gestation (E0) to postnatal day 15 (P15), on voltage-gated sodium channel currents (I(Na)) were investigated in CA1 field of the hippocampus (CA1) neurons using the conventional whole-cell patch-clamp technique on rat hippocampal slices. We found that developmental lead exposure increased the activation threshold and the voltage at which the maximum I(Na) current was evoked, caused positive shifts of I(Na) steady-state activation curve, and enlarged I(Na) tail-currents; Pb(2+) delayed the activation of I(Na) in a voltage-dependent manner, prolonged the time course of the fast inactivation of sodium channels; Pb(2+) induced a right shift of the steady-state inactivation curve, accelerated the activity-dependent attenuation of I(Na), but made no significant effects on the time course of the recovery of I(Na) from inactivation and the fraction of inactivated channels. In addition, the co-treatment with alpha-tocopherol (VE), an effective antioxidant and free radical scavenger, completely prevented the aforementioned changes on I(Na). The alterations on I(Na) properties induced by developmental lead exposure were partly different from that in previous acute experiments under the conditions closer to physiological situation, and the process was considered related to the participating of lead in lipid peroxidation reaction, which has been reported to change the conformation and biophysical functions of membrane proteins.
在本研究中，采用传统的全细胞膜片钳技术，在大鼠海马切片的海马CA1区神经元上，研究了从妊娠第0天（E0）至出生后第15天（P15）期间慢性铅（Pb(2+)）暴露对电压门控钠通道电流（I(Na)）的影响。我们发现，发育过程中的铅暴露增加了激活阈值以及诱发最大I(Na)电流的电压，导致I(Na)稳态激活曲线正向移位，并增大了I(Na)尾电流；Pb(2+)以电压依赖性方式延迟I(Na)的激活，延长钠通道快速失活的时间进程；Pb(2+)诱导稳态失活曲线右移，加速I(Na)的活动依赖性衰减，但对I(Na)从失活状态恢复的时间进程以及失活通道的比例没有显著影响。此外，与有效的抗氧化剂和自由基清除剂α-生育酚（VE）共同处理，完全阻止了上述对I(Na)的变化。发育过程中铅暴露引起的I(Na)特性改变与先前在更接近生理状态条件下的急性实验有所不同，并且该过程被认为与铅参与脂质过氧化反应有关，据报道脂质过氧化反应会改变膜蛋白的构象和生物物理功能。
