Effects of lead on voltage-gated sodium channels in rat hippocampal CA1 neurons.
In this study, the effects of lead (Pb2+) on voltage-gated sodium channel currents (INa) were investigated in acutely dissociated rat hippocampal CA1 neurons using the conventional whole-cell patch-clamp technique. We found that Pb2+ reduced the amplitudes of INa in a concentration-dependent manner, and the effect could be washed out by extracellular application of 3 mM EGTA. The results also showed that at the concentration of 100 microM, Pb2+ decreased the activation threshold and the voltage at which the maximum INa current was evoked and caused negative shifts of INa steady-state activation curve, and enlarged INa tail-currents; Pb2+ induces a left shift of the steady-state inactivation curve, and delayed the recovery of INa from inactivation, and reduced the fraction of available sodium channels; Pb2+ delayed the activation of INa in a concentration- and voltage-dependent manner, and prolonged the time course of the fast inactivation of sodium channels; activity-dependent attenuation of INa was not altered by Pb2+. It was suggested that Pb2+ might exert its effects on sodium channels by binding a specific site on the extracellular side of sodium channels and dragging the IIS4 voltage sensor outwardly. The interaction of Pb2+ with voltage-dependent sodium channels may lead to change in electrical activity and contribute to worsen the neurotoxicological damage.
Gu
Y
Y
School of Life Science, University of Science and Technology of China, Hefei, Anhui 230027, PR China.
Wang
L
L
Xiao
C
C
Guo
F
F
Ruan
D-Y
DY
D000818:Animals; D004305:Dose-Response Relationship, Drug; D006624:Hippocampus / Q000166:cytology* / Q000187:drug effects; D015640:Ion Channel Gating / Q000187:drug effects*; D007854:Lead / Q000633:toxicity*; D008564:Membrane Potentials / Q000187:drug effects; D009474:Neurons / Q000187:drug effects* / Q000502:physiology; D018408:Patch-Clamp Techniques; D051381:Rats; D017208:Rats, Wistar; D015222:Sodium Channels / Q000502:physiology*
D015222:Sodium Channels; D007854:Lead