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

A Menegon, S Pitassi, N Mazzocchi, L Redaelli, R Rizzetto, JF Rolland, C Poli, M Imberti, A Lanati, F Grohovaz

Research output: Contribution to journalArticle

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Abstract

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.
Original languageEnglish
Article number44843
JournalScientific Reports
Volume7
DOIs
Publication statusPublished - 2017

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Ligand-Gated Ion Channels
Pharmaceutical Preparations
Drug Discovery
Fluorescent Dyes
Membrane Potentials
Costs and Cost Analysis
Membranes

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A new electro-optical approach for conductance measurement: An assay for the study of drugs acting on ligand-gated ion channels. / Menegon, A; Pitassi, S; Mazzocchi, N; Redaelli, L; Rizzetto, R; Rolland, JF; Poli, C; Imberti, M; Lanati, A; Grohovaz, F.

In: Scientific Reports, Vol. 7, 44843, 2017.

Research output: Contribution to journalArticle

Menegon, A ; Pitassi, S ; Mazzocchi, N ; Redaelli, L ; Rizzetto, R ; Rolland, JF ; Poli, C ; Imberti, M ; Lanati, A ; Grohovaz, F. / A new electro-optical approach for conductance measurement: An assay for the study of drugs acting on ligand-gated ion channels. In: Scientific Reports. 2017 ; Vol. 7.
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AU - Pitassi, S

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AU - Redaelli, L

AU - Rizzetto, R

AU - Rolland, JF

AU - Poli, C

AU - Imberti, M

AU - Lanati, A

AU - Grohovaz, F

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AB - 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.

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