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 (5x10(-4), 5x10(-5) and 5x10(-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 5x10(-4)g/ml melamine reduced the amplitude of voltage-gated sodium current (I(Na)). At the concentrations of 5x10(-5) and 5x10(-4)g/ml, melamine produced a hyperpolarizing shift in the steady-state activation curve of I(Na) and also enhanced the steady-state inactivate processing of I(Na). 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.
Yang
Jia-Jia
JJ
College of Life Science, Nankai University, 94 Weijin Rd, Nankai District, Tianjin 300071, PR China.
Yang
Zhuo
Z
Zhang
Tao
T
D000200:Action Potentials / Q000187:drug effects*; D000818:Animals; D000833:Animals, Suckling; D056547:CA1 Region, Hippocampal / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D004785:Environmental Pollutants / Q000633:toxicity*; D005506:Food Contamination; D015640:Ion Channel Gating / Q000187:drug effects; D008297:Male; D018408:Patch-Clamp Techniques; D017966:Pyramidal Cells / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D015222:Sodium Channels / Q000378:metabolism*; D014227:Triazines / Q000633:toxicity*
D004785:Environmental Pollutants; D015222:Sodium Channels; D014227:Triazines; C011907:melamine