| Summary: | 碩士 === 國立成功大學 === 生理學研究所 === 100 === Membrane electroporation (MEP) is recognized to exert an increase in the electrical conductivity and permeability of the plasma membrane by use of an externally applied electrical field. Owing to an increase in the transmembrane potential, nanoscale pores can form in the cell membrane, thus allowing molecules to be transported into and out of the cells. Memantine (MEM), a derivative of amantadine, is recognized as an antiviral agent. Previous study indicates that changes in the amount of membrane cholesterol can directly modify the activity of membrane ion channels and membrane properties. The electrical and pharmacological properties of MEP-induced inward current (IMEP) remain largely unknown. In this study, we attempted to use the patch-clamp technique to investigate the properties of IMEP. When cell membrane hyperpolarized, an irregular and transient inward current (IMEP) was clearly elicited. Either LaCl3- (300 μM) or MEM (300 μM) could block this current. In whole cell recording, MEM did not exert any effect on voltage-gated Ca2+ current. In inside-out configuration, MEM applied to either external or internal surface of the excised patch did not suppress the activity of ATP-sensitive K+ channels expressed in GH3 cells. In another series of experiments, our data was showed that depletion of membrane cholesterol by exposing cells to HPCD resulted in reduction of IMEP density. Our study provides the first evidence to show that MEM directly inhibits the amplitude of IMEP in pituitary GH3 cells. MEM-mediated block of IMEP in these cells is unlinked to its inhibition of glutamate-induced currents or ATP-sensitive K+ currents. Deplete of membrane cholesterol by HPCD can alter the pore formation, thereby decreasing the IMEP magnitude. The inhibition of MEM and depletion cholesterol in IMEP might be related to cell function.
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