Neuroscience Institute Cavalieri Ottolenghi (NICO), University of Turin, Regione Gonzole, 10, Orbassano, 10043, Turin, Italy.
J Mol Neurosci. 2012 Mar;46(3):606-15. doi: 10.1007/s12031-011-9648-6. Epub 2011 Sep 13.
In neurons, voltage-dependent Kv3 potassium channels are essential for the generation of action potentials at high frequency. A dysregulation of the Kv3.1 and Kv3.4 channel subunits has been suggested to contribute to neuronal and glial alterations in Alzheimer's disease, but a quantitative evaluation of these subunits in a mouse model of the pathology is still lacking. We analysed the profile of expression of the four Kv3 subunits by quantitative reverse transcription PCR and Western blot in the whole mouse brain and in dissected brain regions (olfactory bulb, septum, neocortex, hippocampus, brainstem and cerebellum) from 14 days after conception to 18 months after birth. In addition, we measured the levels of Kv3.1 and Kv3.4 messenger RNAs (mRNAs) and proteins in neocortex and hippocampus of APPPS1 mice, a transgenic model of Alzheimer's disease. Although all Kv3 transcripts were significantly expressed in embryonic age in whole brain extracts, only Kv3.1, Kv3.2 and Kv3.4 subunit proteins were present, suggesting a novel role for Kv3 channels at this developmental stage. With the exception of Kv3.4, during postnatal development, Kv3 transcripts and proteins showed a progressive increase in expression and reached an asymptote in adulthood, suggesting that the increase in Kv3 expression during development might contribute to the maturation of the electrical activity of neurons. During aging, Kv3 expression was rather stable. In contrast, in the neocortex of aged APPPS1 mice, Kv3.1 mRNA and protein levels were significantly lower compared to wild type, suggesting that a decrease in Kv3 currents could play a role in the cognitive symptoms of Alzheimer's disease.
在神经元中，电压门控 Kv3 钾通道对于高频动作电位的产生至关重要。Kv3.1 和 Kv3.4 通道亚基的失调被认为导致阿尔茨海默病中的神经元和神经胶质改变，但病理小鼠模型中这些亚基的定量评估仍然缺乏。我们通过定量逆转录 PCR 和 Western blot 分析了整个小鼠大脑以及从受孕后 14 天到出生后 18 个月分离的脑区（嗅球、隔区、新皮质、海马、脑干和小脑）中四个 Kv3 亚基的表达谱。此外，我们还测量了 APPPS1 小鼠（阿尔茨海默病的转基因模型）新皮质和海马中 Kv3.1 和 Kv3.4 信使 RNA（mRNA）和蛋白的水平。尽管在整个大脑提取物中，所有 Kv3 转录本在胚胎期都有显著表达，但只有 Kv3.1、Kv3.2 和 Kv3.4 亚基蛋白存在，这表明 Kv3 通道在这个发育阶段具有新的作用。除了 Kv3.4，在出生后发育过程中，Kv3 转录本和蛋白的表达逐渐增加，并在成年期达到一个稳定状态，这表明发育过程中 Kv3 表达的增加可能有助于神经元电活动的成熟。在衰老过程中，Kv3 的表达相对稳定。相比之下，在老年 APPPS1 小鼠的新皮质中，Kv3.1 mRNA 和蛋白水平明显低于野生型，这表明 Kv3 电流的减少可能在阿尔茨海默病的认知症状中起作用。
