期刊
JOURNAL OF NEUROSCIENCE
卷 29, 期 15, 页码 4708-4718出版社
SOC NEUROSCIENCE
DOI: 10.1523/JNEUROSCI.4917-08.2009
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资金
- Belgian Fonds National pour la Recherche Scientifique (FNRS-FRS)
- Communaute Francaise de Belgique
- Actions de Recherche Concertes
- Belgian Fonds de la Recherche Scientifique Medicale
- Fondation pour la Recherche sur la Maladie d'Alzheimer (FRMA)
Synchronous calcium oscillations are observed in primary cultures of rat cortical neurons when mature networks are formed. This spontaneous neuronal activity needs an accurate control of calcium homeostasis. Alteration of intraneuronal calcium concentration is described in many neurodegenerative disorders, including Alzheimer disease (AD). Although processing of amyloid precursor protein (APP) that generates A beta peptide has critical implications for AD pathogenesis, the neuronal function of APP remains unclear. Here, we report that expression of human APP (hAPP) in rat cortical neurons increases L-type calcium currents, which stimulate SK channels, calcium-dependent K+ channels responsible for medium afterhyperpolarization (mAHP). In a neuronal network, increased mAHP in some neurons expressing hAPP leads to inhibition of calcium oscillations in all the cells of the network. This inhibition is independent of production and secretion of A beta and other APP metabolites. In a neuronal network, reduction of endogenous APP expression using shRNA increases the frequency and reduces the amplitude of calcium oscillations. Altogether, these data support a key role for APP in the control of neuronal excitability.
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