Purinergic receptors consist of two main families; P2X and P2Y. P2Y receptors are G protein coupled receptors (GPCR), whereas P2X receptors are non-selective cation channels. P2X7 receptors which is a member of P2X receptors, have been found myriad types of cells including immune cells. The activa-tion of this receptor leads to IL-1β release and caspase activation as well as an increase in membrane permeability to big molecules. Spectroscopic and electrophysiologic methods have been used to in-vestigate membrane permeability. Different hypotheses have been proposed as an explanation for big permeability. One of them proposes that P2X7 channel itself dilates and becomes permeable to big molecules, whereas the other proposes participation of another channels to big permeability. Since it has been demonstrated that P2X7 receptor has a role in many disease processes including inflamation, pain, cancer and Alzheimer’s disease, its antagonists and modulators have been regarded as a good drug target. The uncovering of its activation mechanism is important for treatment of many diseases.

Keywords: P2X7 Receptor, Membrane Permeability, YoPro-1, Lucifer Yellow