PhysioStim Purkinje fiber
PhysioStim Purkinje fiber

Purkinje fiber assays for preclinical safety studies

Action potential recordings can be done using different tissular models. Here at PhysioStim, we use rabbit or dog purkinje fibers, rabbit atria and guinea-pig papillary muscles to answer all your study needs. The sensitivity of action potential assays differs between species and cardiac tissue types. Their selection depends on the ion channels blocked by the compound. Among species and cardiac tissues, action potential recordings in female rabbit Purkinje fibres constitute the most sensitive model to detect the effects of hERG blocking agents on cardiac repolarization. Indeed, inhibition of potassium currents contributing to the terminal phase of repolarisation (phase 3) of the cardiac action potential (IKr / IKs and IK1) is a mechanism by which agents increase APD. These currents are known to contribute to action potential repolarisation in isolated Purkinje fibers.

Technique

  • Conventional intracellular microelectrode technique

Study model

  • Rabbit or dog Purkinje fibres
  • 6 preparations tested and 6 control preparations (as basic design protocol but can be adapted)
  • Options: external hypokaliemic conditions, chronic pre-treatment, incremental stimulation rate

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 or 4 cumulative increasing concentrations of assay compound
  • Stimulation rates: 1 Hz and 0.2 Hz (reverse use dependency)
  • Washout period or positive control at the end of the experiment
Protocol Purkinje Fibers assays

Ref­er­ence compounds

Reference CompoundsConcentration

Quinidine 10 µmol/L

Sotalol 30 µmol/L

Results

Purkinje Fibers assays

Typical effects of sotalol on rabbit Purkinje fibres at 1 and 0.2 Hz.

Additional tests according to PhysioStim scientist’s expertise

Humans cardiomyocites

Human Cardiomyocytes

PhysioStim Isolated Perfused Heart

Isolated perfused heart

hERG assays

PhysioStim Sodium Channel assays

Sodium channel assays

Calcium channel

Calcium channel assays

PhysioStim Potassium Channel assays

Other Potassium channel assays

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