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The Journal of Neuroscience, April 15, 2009, 29(15):4708-4718; doi:10.1523/JNEUROSCI.4917-08.2009

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Neurobiology of Disease
Expression of Human Amyloid Precursor Protein in Rat Cortical Neurons Inhibits Calcium Oscillations

Susana Ferrao Santos,¹ Nathalie Pierrot,¹ Nicole Morel,³ Philippe Gailly,³ Christian Sindic,² and Jean-Noël Octave¹

¹Experimental Pharmacology Unit and ²Neurology Department, Institute of Neuroscience, and ³Laboratory of Cell Physiology, Université catholique de Louvain, B-1200 Brussels, Belgium

Correspondence should be addressed to Jean-Noël Octave, Experimental Pharmacology Unit, Université catholique de Louvain, FARL/UCL 54 10, avenue Hippocrate 54, B-1200 Brussels, Belgium. Email: jean-noel.octave{at}uclouvain.be

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.

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Received Oct. 13, 2008; revised Feb. 12, 2009; accepted Feb. 27, 2009.

Correspondence should be addressed to Jean-Noël Octave, Experimental Pharmacology Unit, Université catholique de Louvain, FARL/UCL 54 10, avenue Hippocrate 54, B-1200 Brussels, Belgium. Email: jean-noel.octave{at}uclouvain.be

This article has been cited by other articles:

				S. Huysseune, P. Kienlen-Campard, S. Hebert, B. Tasiaux, K. Leroy, O. Devuyst, J.-P. Brion, B. De Strooper, and J.-N. Octave Epigenetic control of aquaporin 1 expression by the amyloid precursor protein FASEB J, December 1, 2009; 23(12): 4158 - 4167. [Abstract] [Full Text] [PDF]

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