Effect of melamine on potassium currents in rat hippocampal CA1 neurons.
As an industrially synthesized chemical, melamine has been applied in a wide range of areas. However, many questions on the adverse effect and toxicity of melamine have been emerged, recently. In this investigation, the cytotoxicity of melamine on PC12 cells was evaluated. Furthermore, the effect of melamine on the transient outward potassium current (I(A)) and the delayed rectifier potassium current (I(K)) in hippocampal CA1 pyramidal neurons of rat was studied using whole-cell patch-clamp technique. The results showed that melamine-induced cell death in a concentration and time-dependent manner, and produced a concentration-dependent inhibition in amplitudes of I(A) and I(K) at any concentrations (5x10(-4), 5x10(-5), and 5x10(-6)g/ml). Moreover, at higher concentration (5x10(-4)g/ml), melamine had observable effects of the steady-state inactivation of I(A), that is melamine shifted inactivation curve of I(A) towards hyperpolarization. The spontaneous firing frequency was increased as well. These results suggest that the regulation of I(A) and I(K) induced by melamine would make neurons display aberrant firing properties and abnormal neuronal discharge, which could be a possible underlying mechanism for the melamine-induced neurotoxicity.
Yang
Jia-Jia
JJ
Key Laboratory of Bioactive Materials, Ministry of Education and College of Life Science, Nankai University, Tianjin 300071, PR China.
Tian
Yu-Tao
YT
Yang
Zhuo
Z
Zhang
Tao
T
D000200:Action Potentials / Q000187:drug effects*; D000818:Animals; D056547:CA1 Region, Hippocampal / Q000166:cytology*; D004305:Dose-Response Relationship, Drug; D008297:Male; D009474:Neurons / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D016716:PC12 Cells; D018408:Patch-Clamp Techniques; D015221:Potassium Channels / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D014227:Triazines / Q000633:toxicity*
D015221:Potassium Channels; D014227:Triazines; C011907:melamine