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Assessing hERG channel inhibition using PatchXpress.

Justin Q Ly¹, Gordon Shyy, Dinah L Misner

¹Roche Palo Alto, Department of Non-Clinical Drug Safety, 3431 Hillview Avenue, Palo Alto, CA 94304, USA.

Clinics in Laboratory Medicine

|April 10, 2007

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Automated patch clamp systems can accurately assess human ether-a-go-go related gene (hERG) channel blockers. Using glass-coated plates for compound preparation improved data consistency with conventional methods for hERG channel inhibition.

Area of Science:

Pharmacology
Ion Channel Physiology
Assay Development

Background:

The human ether-a-go-go related gene (hERG) potassium channel is a critical target for drug-induced cardiotoxicity.
Accurate and efficient assessment of hERG channel inhibition is essential for drug safety.
Automated patch clamp (APC) technology offers potential for high-throughput screening of ion channel modulators.

Purpose of the Study:

To evaluate the performance of the PatchXpress automated 16-channel parallel patch clamp system for assessing hERG channel inhibition.
To compare APC results with conventional patch clamp experiments.
To optimize APC assay conditions, including cell harvesting, compound addition, and compound plate material.

Main Methods:

A stable Chinese Hamster Ovary (CHO-K1) cell line expressing hERG channels was generated.

Related Experiment Videos

The PatchXpress system was used for automated 16-channel parallel patch clamp recordings.

Cell harvesting methods (Accumax vs. trypsin) and compound addition strategies (single vs. double) were assessed.

The impact of compound plate material (polystyrene vs. glass-coated) on inhibition data was investigated.

Main Results:

The PatchXpress system successfully determined hERG channel inhibition by known blockers.
Data from APC experiments were comparable to conventional patch clamp recordings.
Cell harvesting and compound addition methods influenced success rates.
For certain compounds, using glass-coated plates for compound preparation yielded inhibition data that more closely matched conventional experimental results.

Conclusions:

The PatchXpress system is a viable tool for automated hERG channel inhibition assays.
Optimization of assay parameters, particularly compound plate material, is crucial for data accuracy.
Glass-coated plates may offer advantages for specific compounds in hERG screening assays.