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Developing High-Throughput Assays to Analyze and Screen Electrophysiological Phenotypes.

Jen Q Pan1, David Baez-Nieto2, Andrew Allen2

  • 1Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA, USA. jpan@broadinstitute.org.

Methods in Molecular Biology (Clifton, N.J.)
|May 9, 2018
PubMed
Summary

High-throughput patch clamping enables scalable analysis of ion channel function. This method facilitates phenotypic screening of voltage-gated calcium channels against genetic variations and drug modulators.

Keywords:
ElectrophysiologyHigh throughputIon channelsPatch clampPhenotypic screenPlanar electrophysiologyVoltage-gated calcium channels

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Area of Science:

  • Biophysics
  • Pharmacology
  • Molecular Biology

Background:

  • Ion channels are crucial drug targets, implicated in numerous human diseases.
  • Traditional ion channel analysis is a bottleneck for large-scale studies.
  • Automated planar electrophysiology advances high-throughput screening.

Purpose of the Study:

  • To describe a methodology for phenotypic screening of ion channels.
  • To enable scalable analysis of voltage-gated calcium channels.
  • To evaluate genetic variations and small-molecule modulators.

Main Methods:

  • Establishing inducible heterologous ion channel expression in HEK293 cells.
  • Utilizing high-throughput planar electrophysiology for functional analysis.
  • Implementing stable and consistent ion channel expression protocols.

Main Results:

  • Demonstrated a scalable method for ion channel functional analysis.
  • Enabled screening across diverse genetic variations of ion channels.
  • Facilitated testing of small-molecule modulators against ion channels.

Conclusions:

  • High-throughput planar electrophysiology democratizes ion channel analysis.
  • The described methodology supports large-scale phenotypic screening.
  • This approach is critical for drug discovery targeting ion channels.