Messenger RNA and protein expression analysis of voltage-gated potassium channels in the brain of Aβ25-35-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. (C) 2004 Wiley-Liss, Inc.