Effects of lead on voltage-gated sodium channels in rat hippocampal CA1 neurons

Abstract

In this study, the effects of lead (Pb 2+) on voltage-gated sodium channel currents (I Na) were investigated in acutely dissociated rat hippocampal CA1 neurons using the conventional whole-cell patch-clamp technique. We found that Pb 2+ reduced the amplitudes of I Na in a concentration-dependent manner, and the effect could be washed out by extracellular application of 3mM EGTA. The results also showed that at the concentration of 100μM, Pb 2+ decreased the activation threshold and the voltage at which the maximum I Na current was evoked and caused negative shifts of I Na steady-state activation curve, and enlarged I Na tail-currents; Pb 2+ induces a left shift of the steady-state inactivation curve, and delayed the recovery of I Na from inactivation, and reduced the fraction of available sodium channels; Pb 2+ delayed the activation of I Na in a concentration- and voltage-dependent manner, and prolonged the time course of the fast inactivation of sodium channels; activity-dependent attenuation of I Na was not altered by Pb 2+. It was suggested that Pb 2+ 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 Pb 2+ with voltage-dependent sodium channels may lead to change in electrical activity and contribute to worsen the neurotoxicological damage.