Purkinje fiber assays for preclinical safety studies

Action Potential Recordings from Purkinje fibers

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.

Why choose PhysioStim for your Purkinje fiber assays ?

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

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

Reference products

  • Quinidine 10 µmol/L
  • Sotalol 30 µmol/L

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
Action Potential Recordings from Purkinje Fibres (Rabbit or Dog)

Measured parameters

  • Resting potential (mV)
  • Action Potential Amplitude (mV)
  • Action Potential Duration at 50%, 70% and 90% of repolarization: APD50, APD70, APD90 (ms)
  • Conduction time (ms)
  • Conduction speed (m/​s)
  • Maximal rate of depolarization: dV/dtmax (V/​s)

Results

Purkinje fiber assay

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

Advice from our expert scientists

In order to confirm the results of your action potential recordings and the impact on electrical activity or ECG, PhysioStim recommends completing your study with additional tests:

Need help with your preclinical safety studies ?

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