The cellular prion protein prevents copper-induced inhibition of P2X ₄ receptors

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 P2X ₄ 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 P2X ₄ receptor when both are coexpressed. PrP ^C expression does not significantly change the ATP concentration-response curve in oocytes expressing P2X ₄ 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⁺.