Characterization Of Selenium-Modulated Effects And Kinetics Research On Rat Dorsal Root Ganglion Neurons

Selenium, as a trace mineral, is an essential nutrient of fundamental importance to human kinds[1]. As a constituent of Selenoproteins, selenium has structural and enzymic roles[2-10]. Selenium may be the most potent nutrient antioxidant, which has been shown to be a very potent anti-carcinogen and anti-mutagen[11,12].Selenium is a promising agent for chemoprevention and chemotherapy of cancer. However, present research data indicate the supranutritional dose and even higher level are necessary for better efficacy. These doses approach toxic dose. Nano-Se, the latest nano-tech production, has high bioavailability and substantial low toxicity, indicating its promising application in chemoprevention and chemotherapy[13]. Little is known, however, about the modulated-effect of Selenium on neuron system. Does it have any effect on human neuronal system by using selenium with low toxic dose for chemoprevention and chemotherapy of cancer?In this research, the characterization of selenium-modulated effect on membrane ion current and channel kinetic were deeply studied, using patch clamp technique on whole cell mode. It indicated that: selenium has no effect on potassium ion current, however, it has significant potential to modulate the sodium ion channel on concentration-dependent and time-dependent way. The sodium current was increased by selenium in nutritional dose, however, decreased by toxic dose. Therefore, the further research on voltage-gated sodium current, including tetrodotoxin-sensitive(TTX-S)and tetrodotoxin-resistant (TTX-R) sodium current has done, which indicated that selenium increased and decreased the TTX-S sodium current markedly, however, has not significant effect on TTX-R sodium current. According to what was mentioned above, we focus on the research of the low toxic dose selenium-modulated effect and channel kinetics on TTX-S voltage-dependent sodium current in rat dorsal root ganglion neurons (DRG). By analyzing the data of conductance, I-V relationship and kinetics study such as steady-state activation, inactivation and recovery curve, we got the the results which proved that selenium acted within the channel pore, not on or near the exterior surface of the channelprotein where it would experience the membrane electric field. Finally, the comparative research between nano-se and selenite indicated the conclusion and reasonable hypothesizes, including that:1) The short-term toxic of Nano-Se was significantly lower than that of selenite, with high bioavailability, indicating its promising application in chemoprevention and chemotherapy; 2) Nano-Se and selenite possess the same competitive binding site;3) Nano-Se and selenite possess different binding sites and there is negative allosteric interaction between these two binding sites.