Developmental exposure to lead causes inherent changes on voltage-gated sodium channels in rat hippocampal CA1 neurons.
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.
Yan
D
D
School of Life Science, University of Science and Technology of China, Hefei, Anhui, PR China.
Wang
L
L
Ma
F-L
FL
Deng
H
H
Liu
J
J
Li
C
C
Wang
H
H
Chen
J
J
Tang
J-L
JL
Ruan
D-Y
DY
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D005260:Female; D006624:Hippocampus / Q000166:cytology / Q000187:drug effects* / Q000473:pathology*; D066298:In Vitro Techniques; D007854:Lead / Q000378:metabolism; D007855:Lead Poisoning / Q000473:pathology*; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D009474:Neurons / Q000187:drug effects* / Q000473:pathology*; D018408:Patch-Clamp Techniques; D051381:Rats; D017208:Rats, Wistar; D026941:Sodium Channel Blockers / Q000494:pharmacology; D015222:Sodium Channels / Q000187:drug effects*; D014810:Vitamin E / Q000494:pharmacology
D000975:Antioxidants; D026941:Sodium Channel Blockers; D015222:Sodium Channels; D014810:Vitamin E; D007854:Lead