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+).