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Updated: Jun 28, 2026
Voltage-Dependent Potassium Current Recording on H9c2 Cardiomyocytes via the Whole-Cell Patch-Clamp Technique
Published on: November 11, 2022
Recording hERG potassium currents and assessing the effects of compounds using the whole-cell patch-clamp technique
1Millipore, Cambridge, UK.
Insights
The human Ether-à-go-go-Related Gene (hERG) channel is crucial for heart rhythm. Blocking this channel can cause dangerous arrhythmias like Torsades de Pointes, necessitating reliable testing methods.
Area of Science:
- Cardiovascular Pharmacology
- Ion Channel Physiology
- Cardiac Electrophysiology
Background:
- The human Ether-à-go-go-Related Gene (hERG) channel is essential for cardiac repolarization.
- Dysfunctional hERG channels or blockade can lead to arrhythmias such as Torsades de Pointes (TdP).
- Assessing drug effects on hERG currents is critical for cardiotoxicity evaluation.
Purpose of the Study:
- To describe a method for recording hERG currents in a recombinant cell line.
- To present voltage protocols for assessing hERG channel properties and drug interactions.
- To provide a framework for reliable in vitro assessment of hERG channel blockers.
Main Methods:
- Whole-cell patch-clamp technique applied to a recombinant cell line expressing hERG channels.
- Utilization of specific voltage-clamp protocols to elicit and measure hERG currents.
- Application of protocols to assess the impact of compounds on hERG tail currents.
Main Results:
- Established a reliable method for recording hERG currents using whole-cell patch-clamp.
- Demonstrated the utility of specific voltage protocols for characterizing hERG channel function.
- Showcased the application of these protocols for evaluating drug-induced hERG current inhibition.
Conclusions:
- The described whole-cell patch-clamp method and voltage protocols are effective for studying hERG channel function.
- This approach provides a robust platform for assessing the cardiotoxic potential of drug candidates by evaluating their effects on hERG channels.
- Accurate assessment of hERG channel activity is vital for drug safety and preventing cardiac arrhythmias.
Abstract:
The complex gating of the hERG channel makes it ideally suited to its principal role in controlling phase 3 repolarization of the cardiac ventricular action potential. Any abnormal delay in repolarization can lead to the re-activation of Ca(2)+ channels, giving rise to early after-depolarizations, and coupled with increased cardiac dispersion, typically associated with these delays, provides respectively both the trigger and substrate for the potentially life threatening arrhythmia Torsardes de Pointes (TdP). Owing to the fundamental role of hERG in controlling the duration of the cardiac action potential, it is not surprising that any drugs that potently and selectively block this channel are liable to have these effects. Consequently, much effort has been expended in developing standard voltage protocols to reliably assess the effects of compounds on hERG currents in vitro. This chapter describes how to record hERG currents in a recombinant cell line using the whole-cell patch-clamp technique. It also provides typical voltage protocols used for assessing the basic electrophysiological properties of these currents and for assessing the effects of compounds on hERG tail currents.
