High-Throughput Screening for Ion Channel Modulators

Author:

Falconer Margaret1,Smith Fiona2,Surah-Narwal Sandha2,Congrave Gill3,Liu Zhen2,Hayter Paul2,Ciaramella Giuseppe2,Keighley Wilma1,Haddock Peter3,Waldron Gareth2,Sewing Andreas1

Affiliation:

1. Lead Discovery Technologies, Pfizer Global Research and Development, Sandwich, United Kingdom

2. Hit Discovery Group, Pfizer Global Research and Development, Lead Discovery Technologies, Sandwich, United Kingdom

3. Cardiovascular Biology, Pfizer Global Research and Development, Lead Discovery Technologies, Sandwich, United Kingdom

Abstract

Ion channels present a group of targets for major clinical indications, which have been difficult to address due to the lack of suitable rapid but biologically significant methodologies. To address the need for increased throughput in primary screening, the authors have set up a Beckman/Sagian core system to fully automate functional fluorescence-based assays that measure ion channel function. They apply voltage-sensitive fluorescent probes, and the activity of channels is monitored using Aurora's Voltage/Ion Probe Reader (VIPR). The system provides a platform for fully automated high-throughput screening as well as pharmacological characterization of ion channel modulators. The application of voltage-sensitive fluorescence dyes coupled with fluorescence resonance energy transfer is the basis of robust assays, which can be adapted to the study of a variety of ion channels to screen for both inhibitors and activators of voltage-gated and other ion channels.

Publisher

Elsevier BV

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