The ATP-gated P2X7 receptor channel operates as a cytolytic and apoptotic receptor but also controls sustained cellular responses, including cell growth, proliferation and secretion. Experimental data suggest that that aromatic residues in the upper part of the first transmembrane domain are critical for both the P2X7R channel pore opening and receptor sensitization, and residues located at or below the intersection of the second transmembrane domains control its conductivity.