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Related Experiment Videos

Identifying modulators of hERG channel activity using the PatchXpress planar patch clamp.

Adrienne E Dubin1, Nadia Nasser, Jutta Rohrbacher

  • 1Pain and Related Disorders, Johnson and Johnson Pharmaceutical Research and Development, San Diego, CA 92121, USA. adubin@prdus.jnj.com

Journal of Biomolecular Screening
|April 1, 2005
PubMed
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The PatchXpress system effectively measures compound activity at the hERG channel, offering a faster alternative to traditional methods. It accurately identifies drug candidates, accelerating ion channel modulator discovery.

Area of Science:

  • Pharmacology
  • Electrophysiology
  • Drug Discovery

Background:

  • The hERG channel is a critical target for drug safety assessment due to its role in cardiac repolarization.
  • Conventional whole-cell patch clamp is the gold standard for measuring hERG channel activity but is time-consuming and labor-intensive.
  • There is a need for high-throughput, reliable methods to screen compounds for hERG channel activity.

Purpose of the Study:

  • To evaluate the performance of the PatchXpress 7000A system for measuring compound activity at the hERG channel.
  • To compare the PatchXpress system's results with conventional whole-cell patch clamp methods.
  • To assess the utility of the PatchXpress system in accelerating drug discovery for ion channel modulators.

Main Methods:

  • Utilized the PatchXpress 7000A system to perform electrophysiological measurements on hERG302-HEK cells.

Related Experiment Videos

  • Tested a set of 70 compounds, including hERG antagonists with varying potencies.
  • Employed protocols for single-concentration activity identification and cumulative concentration-dependent potency determination.
  • Included compound washout steps to assess reversibility and used a reference compound for quality control.

    • Main Results:

    • Electrical parameters and voltage dependence obtained with PatchXpress were comparable to conventional patch clamp.
    • The rank order of compound potency determined by PatchXpress correlated well with conventional methods, with one exception (flunarizine).
    • PatchXpress successfully identified 29 moderately potent antagonists missed by binding assays, demonstrating improved sensitivity.
    • No false positive hits were observed from inactive compounds.

    Conclusions:

    • The PatchXpress 7000A system provides high-quality data for hERG channel compound activity assessment.
    • The system mimics conventional patch clamp performance, offering a more efficient alternative.
    • PatchXpress has the potential to significantly accelerate secondary screening and the overall drug discovery process for ion channel modulators.