Messenger RNA and protein expression analysis of voltage-gated potassium channels in the brain of Abeta(25-35)-treated rats.
Potassium channel dysfunction has been implicated in Alzheimer's disease. In the present study, the expression of voltage-gated potassium channel (Kv) subunits in rat brain was measured after a single intracerebroventricular injection of beta-amyloid peptide 25-35 (Abeta(25-35)). After injection of Abeta, the spatial memory of rats was significantly impaired in the Morris water maze. Expression of five main Kv channel subunits (Kv1.5, Kv2.1, Kv1.4, Kv4.2, and Kv4.3) in mRNA level was assessed by using reverse transcription-polymerase chain reaction (RT-PCR). The mRNA levels of Kv2.1 and Kv1.4 were increased by 72% and 67%, respectively, in hippocampus, and Kv4.2 mRNA was increased by 58% in cortex. No other significant mRNA expression changes were found in Abeta-treated rats. The protein expression of Kv2.1, Kv1.4, and Kv4.2 was detected by using Western blotting. Kv2.1 and Kv1.4 protein levels were increased by 48% and 50%, respectively, in hippocampus of Abeta-treated rats, and Kv4.2 protein was increased by 42% in cerebral cortex. This study indicates that the expression up-regulation of Kv1.4, Kv2.1, and Kv4.2 in Abeta-induced cognitive impairment might play an important role in the pathogenesis of Alzheimer's disease.
Pan
Yaping
Y
Department of Pharmacology, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
Xu
Xianghua
X
Tong
Xiaoyong
X
Wang
Xiaoliang
X
D000544:Alzheimer Disease / Q000378:metabolism* / Q000503:physiopathology; D016229:Amyloid beta-Peptides / Q000378:metabolism* / Q000494:pharmacology; D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism* / Q000503:physiopathology; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology; D051668:Delayed Rectifier Potassium Channels; D004195:Disease Models, Animal; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology; D007276:Injections, Intraventricular; D051665:Kv1.4 Potassium Channel; D051666:Kv1.5 Potassium Channel; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D008569:Memory Disorders / Q000139:chemically induced / Q000235:genetics / Q000378:metabolism; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D010446:Peptide Fragments / Q000378:metabolism* / Q000494:pharmacology; D015221:Potassium Channels / Q000235:genetics / Q000378:metabolism; D024642:Potassium Channels, Voltage-Gated / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D051669:Shab Potassium Channels; D051672:Shal Potassium Channels; D015854:Up-Regulation / Q000187:drug effects / Q000235:genetics
D016229:Amyloid beta-Peptides; D051668:Delayed Rectifier Potassium Channels; C496979:Kcna4 protein, rat; C496983:Kcna5 protein, rat; C496991:Kcnb1 protein, rat; C497020:Kcnd2 protein, rat; C497023:Kcnd3 protein, rat; D051665:Kv1.4 Potassium Channel; D051666:Kv1.5 Potassium Channel; D010446:Peptide Fragments; D015221:Potassium Channels; D024642:Potassium Channels, Voltage-Gated; D012333:RNA, Messenger; D051669:Shab Potassium Channels; D051672:Shal Potassium Channels; C074636:amyloid beta-protein (25-35)