hERG cardiac ion channel

hERG (human Ether à-go-go Related Gene)

ICH level: mandatory study according to ICH S7B

hERG assays are essential to study the cardiovascular safety of a new drug or compound. It’s the pore forming subunit of a potassium ion channel that conducts the rapid component of the delayed rectifier potassium current known as IKr. This ion channel contributes to the repolarization phase of the action potential. When the hERG channel cannot adequately conduct electrical current across the cell membrane, this can result in a potentially fatal disorder called type 2 long QT syndrome (LQT2).

The experts at PhysioStim respect all ICH guidelines to perform screening or GLP-compliant safety studies. Moreover, our stimulation protocol is designed to make sure you get the highest value out of your assay:

hERG assays & preclinical safety studies

Preclinical hERG assays aim to identify potential inhibitory effects early in drug discovery. Current ICH Guidelines state that hERG assays are mandatory, as a number of clinically successful drugs have had the tendency to inhibit hERG and create a concomitant risk of sudden death. As a result, a large number of drugs have been withdrawn from the market or during late stage clinical trials due to cardiotoxic effects.

What is shown?

Inhibition of the hERG channel by pharmaceutical substances is the primary cause of drug-induced QT prolongation. IKr current inhibition has been shown to prolong the cardiac action potential duration, a phenomenon associated with increased risk of QT interval prolongation. This can lead to potentially fatal ventricular tachyarrhythmia, known as Torsades de pointe.


  • Patch Clamp
  • 3 or 4 increasing cumulative
    concentrations of assay compound
  • Experiment conducted at room temperature or at physiological temperature (35°C)

Study model

  • Human Embryonic Kidney HEK-293 cells
  • 5 treated cells and 5 control cells (as basic design protocol but can be adapted)

Measured parameters

  • Amplitude of the tail current upon repolarization to -40 mV (pA)
  • Amplitude of the base current at -80 mV (pA)
  • Inhibition of hERG tail current (%)
  • Ion current inhibition measurement
  • IC50 value

Stimulation protocol

herg protocol
herg assay protocol

Typical concentration-dependent effects of cisapride on IKr currents recorded from HEK-293 cells.

Ref­er­ence com­pounds or pos­i­tive con­trols

Reference Compounds hERGIC₅₀

E–403132.3 nM

Dofetilide10.8 nM

Fle­caïnide1.0 µM

Sotalol69.0 µM

Bepridil0.3 µM

Amio­darone27.9 nM

Quini­dine0.3 µM

Ziprasi­done0.2 µM

Cis­apride26.1 nM

Verapamil0.3 µM

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