Papillary muscle assays for preclinical safety studies
Action potential recordings can be obtained using different tissular models. The sensitivity of action potential assays differs between species and cardiac tissue types. Their selection depends on the ion channels blocked by the compound. Here at PhysioStim, we use guinea-pig papillary muscles, rabbit atria and rabbit or dog purkinje fibers to answer all your study needs. Isolated papillary muscles from guinea-pigs are among the standard experimental preparations in cardiovascular research. This model also allows to investigate the effects of drugs on KvLQT1/MinK channels, available in this species.
Technique
- Conventional intracellular microelectrode technique
Study model
- Guinea-pig papillary muscle
- 6 preparations tested and 6 control preparations (as basic design protocol but can be adapted)
Measured parameters
- Resting potential (mV)
- Action Potential Amplitude (mV)
- Action Potential Duration at 50%, 70% and 90% of repolarization: APD50, APD70, APD90 (ms)
- Maximal rate of depolarization: dV/dtmax (V/s)
Stimulation protocol
- 3 cumulative increasing concentrations of assay compound
- Stimulation rates: 1, 0.5 and 2 Hz (reverse use dependency)
- Washout period or positive control at the end of the experiment
Results
Typical effects of veratridine on guinea-pig papillary muscles at 1 Hz.
Reference compounds
Reference compoundsConcentration
Veratridine1 µmol/L
