PT  - JOURNAL ARTICLE
AU  - Susana Ferrao Santos
AU  - Nathalie Pierrot
AU  - Nicole Morel
AU  - Philippe Gailly
AU  - Christian Sindic
AU  - Jean-Noël Octave
TI  - Expression of Human Amyloid Precursor Protein in Rat Cortical Neurons Inhibits Calcium Oscillations
AID  - 10.1523/JNEUROSCI.4917-08.2009
DP  - 2009 Apr 15
TA  - The Journal of Neuroscience
PG  - 4708--4718
VI  - 29
IP  - 15
4099  - http://www.jneurosci.org/content/29/15/4708.short
4100  - http://www.jneurosci.org/content/29/15/4708.full
SO  - J. Neurosci.2009 Apr 15; 29
AB  - 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 Aβ 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 Aβ 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.