Action Potential Recordings from Purkinje Fibres (Rabbit or Dog)
Rabbit: the most sensitive model to study QT prolongation
|Standard Protocol for GLP studies:
- six preparations
- Four cumulative increasing concentrations of assay compound
- Washout period or positive control at the end of the experiment
- Stimulation rates: 1 Hz and 0.2 Hz (reverse use dependency)
Treated groups could be compared to a control vehicle group performed in the same conditions.
Options: External hypokaliemic conditions, chronic pre-treatment, incremental stimulation rate.
- Resting potential (RP) (mV)
- Maximal rate of depolarization (dV/dtmax) (V/s)
- Action Potential Amplitude (APA) (mV)
- Action Potential Duration at 50%, 70% and 90% of repolarization (ms) = APD50, APD70, APD90
APD90 – 40, APD40 if necessary (triangulation)