Ligand gated ion channels are involved in many pathophysiological processes and represent a relevant, although challenging, target for drug discovery. We propose an innovative electro-optical approach to their analysis able to derive membrane conductance values from the local membrane potential changes imposed by test current pulses and measured by fast voltage-sensitive fluorescent dyes. We exploited the potential of this proprietary method by developing a drug testing system called "ionChannel Optical High-content Microscope" (ionChannelω). This automated platform was validated by testing the responses of reference drugs on cells expressing different ligand-gated ion channels. Furthermore, a double-blind comparison with FLIPR and automated patch-clamp was performed on molecules designed to act as antagonists of the P2RX7 receptor. ionChannelω proved highly reliable in all tests, resulting faster and more cost-effective than electrophysiological techniques. Overall, ionChannelω is amenable to the study of ligand gated ion channels that are receiving less attention due to limitations in current assays. © 2017 The Authors.
Menegon, A., Pitassi, S., Mazzocchi, N., Redaelli, L., Rizzetto, R., Rolland, JF., Poli, C., Imberti, M., Lanati, A., & Grohovaz, F. (2017). A new electro-optical approach for conductance measurement: An assay for the study of drugs acting on ligand-gated ion channels. Scientific Reports, 7, . https://doi.org/10.1038/srep44843