Biphasic effects of copper on neurotransmission in rat hippocampal neurons

Christian Peters, Braulio Muñoz, Fernando J. Sepúlveda, Juan Urrutia, Mauricio Quiroz, Sandra Luza, Giancarlo V. De Ferrari, Luis G. Aguayo, Carlos Opazo

Resultado de la investigación: Contribución a una revistaArtículo

42 Citas (Scopus)

Resumen

The importance of copper in the CNS is well documented, but the mechanisms related to its brain functions are poorly understood. Copper is released at the synaptic cleft, where it may modulate neurotransmission. To understand the functional impact of copper on the neuronal network, we have analyzed the synaptic activity of primary rat hippocampal neurons by using different approaches including whole cell patch clamp, recording of calcium transients, immunofluorescence and western blot. Here, we show that copper produces biphasic changes in neurotransmission. When copper is acutely applied to the plate it blocks neurotransmission. Interestingly, when it is applied for 3 h to hippocampal neurons it mainly increases the frequency and amplitude of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)ergic currents (control: 0.21 ± 0.05 Hz/22.9 ± 1.3 pA; copper: 0.68 ± 0.16 Hz/30.5 ± 2.5 pA), intracellular calcium transients (control: 0.05 ± 0.013 Hz; copper: 0.11 ± 0.02 Hz) and evoked AMPA currents (control: EC50 8.3 ± 0.5 μM; copper: EC50 2.9 ± 0.2 μM). Moreover, our results suggest that copper increases GluA1 subunit levels of the AMPA receptor through the anchorage of AMPA receptors to the plasma membrane as a result of PSD-95 accumulation. We also found that copper-treated neurons displayed an undistinguishable neurotransmission to control neurons after 24 h of treatment, indicating that changes in neurotransmission induced by copper at 3 h of incubation are homeostatically regulated after long-term exposure to the metal. Together, our data reveal an unexpected biphasic effect of copper on neurotransmission, which may be relevant to understand the effects of this ion in brain diseases that display copper dyshomeostasis such as that observed in Alzheimer's disease (AD).

Idioma originalInglés
Páginas (desde-hasta)78-88
Número de páginas11
PublicaciónJournal of Neurochemistry
Volumen119
N.º1
DOI
EstadoPublicada - oct 2011

Áreas temáticas de ASJC Scopus

  • Bioquímica
  • Neurociencia celular y molecular

Huella Profundice en los temas de investigación de 'Biphasic effects of copper on neurotransmission in rat hippocampal neurons'. En conjunto forman una huella única.

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    Peters, C., Muñoz, B., Sepúlveda, F. J., Urrutia, J., Quiroz, M., Luza, S., De Ferrari, G. V., Aguayo, L. G., & Opazo, C. (2011). Biphasic effects of copper on neurotransmission in rat hippocampal neurons. Journal of Neurochemistry, 119(1), 78-88. https://doi.org/10.1111/j.1471-4159.2011.07417.x