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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.

A new electro-optical approach for conductance measurement: an assay for the study of drugs acting on ligand-gated ion channels