The Cellular Prion Protein Prevents Copper-Induced Inhibition of P2X4 Receptors. (19th October 2011)

• Record Type: Journal Article
• Authors: Lorca, Ramón A.; Varela-Nallar, Lorena; Inestrosa, Nibaldo C.; Huidobro-Toro, J. Pablo
• Other Names: Squitti Rosanna Academic Editor.
• Is Part Of: International journal of alzheimer's disease. Volume 2011(2011)
• Publication Date: 2011-10-19
• Subjects: Alzheimer's disease -- Periodicals; 616.831005
• DOI: 10.4061/2011/706576
• Languages: English
• ISSNs: 2090-8024

Abstract

Abstract : Although the physiological function of the cellular prion protein (PrP C ) remains unknown, several evidences support the notion of its role in copper homeostasis. PrP C binds Cu 2+ through a domain composed by four to five repeats of eight amino acids. Previously, we have shown that the perfusion of this domain prevents and reverses the inhibition by Cu 2+ of the adenosine triphosphate (ATP)-evoked currents in the P2X4 receptor subtype, highlighting a modulatory role for PrP C in synaptic transmission through regulation of Cu 2+ levels. Here, we study the effect of full-length PrP C in Cu 2+ inhibition of P2X4 receptor when both are coexpressed. PrP C expression does not significantly change the ATP concentration-response curve in oocytes expressing P2X4 receptors. However, the presence of PrP C reduces the inhibition by Cu 2+ of the ATP-elicited currents in these oocytes, confirming our previous observations with the Cu 2+ binding domain. Thus, our observations suggest a role for PrP C in modulating synaptic activity through binding of extracellular Cu 2+ .