Mouse parotid acinar cells express P2X(4) and P2X(7) receptors (mP2X(4)R and mP2X(7)R) whose physiological function remains undetermined. Here we show that mP2X(4)R expressed in HEK-293 cells do not allow the passage of tetraethylammonium (TEA(+)) and promote little, if any, ethidium bromide (EtBr) uptake when stimulated with ATP or BzATP. In contrast, mP2X(7)R generates slowly decaying TEA(+) current, sustained Na+ current and promotes robust EtBr uptake. However, ATP-activated TEA(+) current from acinar cells was unlike that generated by mP2X(7)R or mP2X(4)R. Functional interactions between mP2X(4)R and mP2X(7)R were investigated in HEK cells co-transfected with different mP2X(4) : mP2X(7) cDNA ratios and using solutions containing either TEA(+) or Na+ ions. Co-expressed channels generated a TEA(+) current that displayed faster decay during ATP stimulation than mP2X(7)R alone. Moreover, cells transfected with a 2 : 1 cDNA ratio displayed decaying kinetics similar to those observed in acinar cells. Concentration-response curves in Na+-containing solutions were constructed for heterologously expressed mP2X(4)R, mP2X(7)R and mP2X(4)R: mP2X(7)R co-expressions as well as acinar cells. The EC50 values determined were 11, 220, 434 and 442 mu M, respectively. Na+ currents generated by expressing mP2X(4)R or mP2X(7)R alone were potentiated by ivermectin (IVM). In contrast, IVM potentiation in acinar cells and HEK cells co-expressing P2X(4) and P2X(7) (1 : 1 or 2 : 1 cDNA ratios) was seen only when the ATP concentration was lowered from 5 to 0.03 mM. Taken together our observations indicate a functional interaction between murine P2X(7) and P2X(4) receptors. Such interaction might occur in acinar cells to shape the response to extracellular ATP in salivary epithelia.
