Allosteric Interactions in P2X Receptor Subunits

P2X receptors represent the third superfamily of ligand gated ion channels with ATP as their natural ligand. In spite of them being an attractive drug target, their potential as a drug target is limited by the lack of basic understanding of the structure-function relationship of these receptors. In this work, I have investigated the behaviour of homomeric P2X receptor subunits with the help of photolabeling and fluorescence techniques coupled with electrophysiological measurements using Xenopus laevis oocytes heterologous expression system. Photolabeling system offered real time labelling of P2X receptors and concurrent measurement of current from the same set of receptors. Also, this study for the first time describes the agonist potency of Alexa-ATP (a fluorescent ATP analogue) on P2X1 receptors. Using these technologies, it was found that the receptor subunits are not independent but interacting with each other in a cooperative manner. This work has attempted to answer few intriguing questions in the field of P2X receptor research and I think that the answers provide many avenues to the basic understanding of the functioning of P2X receptors.