Structural and functional alterations in mitochondrial membrane in picrotoxin-induced epileptic rat brain

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• 作者：Acharya ; Munjal M. ; Katyare ; Surendra S.
• 关键词：Picrotoxin ; Epilepsy ; Mitochondria ; ATPase ; Oxidative phosphorylation ; Membrane fluidity ; Cytochromes ; Phospholipids profile
• 刊名：Experimental Neurology
• 出版年：2005
• 期刊代码：78_00144886
• 类别：neu
• 出版时间：March, 2005
• 卷：192
• 期：1
• 页码：79-88
• 文件大小：291 K

摘要

Mitochondrial function is a key determinant of both excitability and viability of neurons. Present studies were carried out to decipher cerebral mitochondrial oxidative energy metabolism and membrane function in the chronic condition of generalized seizures induced by picrotoxin (PTX) in rats. PTX-induced convulsions resulted in decreased respiration rates (14芒芒芒41%) with glutamate, pyruvate + malate, and succinate as substrate. The ADP phosphorylation rates were drastically reduced by 44芒芒芒65%. An opposite trend was observed with ascorbate + N,N芒芒芒,N芒芒芒-tetramethyl-p-phenylenediamine (TMPD) as substrate. In general, uncoupling of the mitochondrial electron transport was observed after PTX treatment. Malate dehydrogenase (MDH) and succinate dehydrogenase (SDH) activities were decreased by 20芒芒芒80%; also, there was significant reduction in cytochrome b content after PTX treatment, while the F_oF₁ ATPase (complex V) activity increased in basal and 2,4-dinitrophenol (DNP)-stimulated condition, indicating increased membrane fragility. The substrate kinetics analysis had shown that K_m and V_max of the higher affinity kinetic component of ATPase increased significantly by 1.2- to 1.4-fold in epileptic condition. Temperature kinetic analysis revealed 1.2-fold increase in energies of activation with decreased transition temperature. The total phospholipid (TPL) and cholesterol (CHL) contents decreased significantly with lowering of diphosphatidylglycerol (DPG), phosphatidylethanolamine (PE), phosphatidylinositol (PI), and phosphatidylserine (PS), while lysophospholipid (lyso), sphingomyelin (SPM), and phosphatidylcholine components were found to be elevated. Brain mitochondrial membrane was somewhat more fluidized in epileptic animals. Possible consequences of mitochondrial respiratory chain (MRC) dysfunction are discussed. In conclusion, impairment of MRC function along with structural alterations suggests novel pathophysiological mechanisms important for chronic epileptic condition.