Functional Studies of Sodium Channels: From Target to Compound Identification

Daniel Bertrand1, Bruno Biton2, Thomas Licher2, Jean‐Marie Chambard2, Christophe Lanneau2, Michel Partiseti2, Isabel A. Lefevre2

1 HiQScreen, Geneva, 2 Sanofi, Paris
Publication Name:  Current Protocols in Pharmacology
Unit Number:  Unit 9.21
DOI:  10.1002/cpph.14
Online Posting Date:  December, 2016
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Over the last six decades, voltage‐gated sodium (Nav) channels have attracted a great deal of scientific and pharmaceutical interest, driving fundamental advances in both biology and technology. The structure and physiological function of these channels have been extensively studied; clinical and genetic data have uncovered their implication in diseases such as epilepsy, arrhythmias, and pain, bringing them into focus as current and future drug targets. While different techniques have been established to record the activity of Nav channels, proper determination of their properties still presents serious challenges, depending upon the experimental conditions and the desired subtype of channel to be characterized. The aim of this unit is to review the characteristics of Nav channels, their properties, the cells in which they can be studied, and the currently available techniques. Topics covered include the determination of Nav‐channel biophysical properties as well as the use of toxins to discriminate between subtypes using electrophysiological or optical methods. Perspectives on the development of high‐throughput screening assays with their advantages and limitations are also discussed to allow a better understanding of the challenges encountered in voltage‐gated sodium channel preclinical drug discovery. © 2016 by John Wiley & Sons, Inc.

Keywords: voltage‐gated sodium channels; screening; electrophysiology; high throughput; fluorescent readout

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Table of Contents

  • Introduction
  • Techniques and Platforms
  • Electrophysiology Proficiencies and Critical Parameters
  • Biological Tools
  • Pharmacology of Nav Channels
  • Sodium Channel Blockers
  • From HTS to Manual Patch: Tools, Techniques, and Strategies
  • Overview and Perspectives
  • Literature Cited
  • Figures
  • Tables
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PDF or HTML at Wiley Online Library



Literature Cited

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