Action potential changes associated with impairment of functional properties of sodium channels in hippocampal neurons induced by melamine

Since the melamine-contamination event happened in September 2008, there have been lots of studies about melamine toxicity, but very limited studies focused on central nervous system (CNS). In the present study, we investigated the effects of melamine (5 × 10−4, 5 × 10−5 and 5 × 10−6 g/ml) on voltage-gated sodium channels (VGSCs) in hippocampal CA1 neurons using whole-cell patch-clamp recordings technique. The results showed that only 5 × 10−4 g/ml melamine reduced the amplitude of voltage-gated sodium current (INa). At the concentrations of 5 × 10−5 and 5 × 10−4 g/ml, melamine produced a hyperpolarizing shift in the steady-state activation curve of INa and also enhanced the steady-state inactivate processing of INa. Action potential properties and the pattern of repetitive firing were examined using current-clamp recording, which indicated that peak amplitude and overshoot of the evoked single action potential were decreased. The half-width and the firing rate of repetitive firing were increased in a concentration-dependent manner. The data suggest that melamine alters the action potential of hippocampal CA1 neurons by impairing the functional properties of VGSCs, which may be the underlie mechanisms of neurotoxicity induced by melamine.