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Published on: March 23, 2011
Developmental exposure to lead causes inherent changes on voltage-gated sodium channels in rat hippocampal CA1
1School of Life Science, University of Science and Technology of China, Hefei, Anhui, PR China.
Insights
Developmental lead exposure alters sodium channel function in rat hippocampus neurons. Alpha-tocopherol (VE) treatment prevented these lead-induced changes, suggesting a role for oxidative stress.
Area of Science:
- Neuroscience
- Toxicology
- Biophysics
Background:
- Developmental exposure to lead (Pb(2+)) is a significant public health concern.
- Lead toxicity can affect neuronal function and development.
- Voltage-gated sodium channels (I(Na)) are critical for neuronal excitability.
Purpose of the Study:
- To investigate the chronic effects of developmental lead exposure on I(Na) properties in rat hippocampal CA1 neurons.
- To determine if alpha-tocopherol (VE) can mitigate lead-induced alterations in I(Na).
Main Methods:
- Whole-cell patch-clamp technique on rat hippocampal slices.
- Chronic lead exposure from gestation day 0 to postnatal day 15.
- Co-treatment with alpha-tocopherol (VE).
Main Results:
- Developmental lead exposure shifted I(Na) activation and inactivation curves.
- Lead exposure altered I(Na) activation kinetics and prolonged fast inactivation.
- Lead exposure accelerated activity-dependent I(Na) attenuation but did not affect recovery from inactivation.
- Alpha-tocopherol (VE) completely prevented lead-induced changes in I(Na).
Conclusions:
- Developmental lead exposure significantly alters I(Na) properties in hippocampal neurons.
- These alterations may be linked to lead-induced lipid peroxidation.
- Alpha-tocopherol (VE) offers neuroprotection against lead-induced sodium channel dysfunction.
Abstract:
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.
