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Nonlinear effects in subthreshold virtual electrode polarization.

Aleksandre T Sambelashvili1, Vladimir P Nikolski, Igor R Efimov

  • 1Department of Biomedical Engineering, Case Western Reserve University, Cleveland, Ohio 44106-7207, USA.

American Journal of Physiology. Heart and Circulatory Physiology
|May 14, 2003
PubMed
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Virtual electrode polarization (VEP) theory explains heart electrophysiology puzzles. This study confirms VEPs exist at all stimulus strengths, even subthreshold levels during diastole, challenging prior beliefs.

Area of Science:

  • Cardiovascular Physiology
  • Computational Biology
  • Biophysics

Background:

  • The virtual electrode polarization (VEP) theory offers explanations for long-standing questions in cardiac electrophysiology, including stimulation and defibrillation mechanisms.
  • Bidomain theory posits that VEPs occur at all stimulus strengths, but their presence at subthreshold levels during diastole is debated.

Purpose of the Study:

  • To investigate the existence and characteristics of cardiac membrane polarization caused by subthreshold stimuli.
  • To determine if VEPs are present during diastole at subthreshold stimulus strengths.

Main Methods:

  • Utilized high-resolution fluorescent imaging with the voltage-sensitive dye di-4-ANEPPS in rabbit ventricular muscle.
  • Employed an active bidomain model incorporating Luo-Rudy ion channel kinetics for in silico analysis.

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Main Results:

  • Both in vitro and in silico models demonstrated the presence of the characteristic dog-bone-shaped VEP at all stimulus strengths, during both systole and diastole.
  • Diastolic subthreshold VEPs displayed nonlinear behavior, including time-dependent asymmetric reversal of membrane polarization relative to stimulus polarity.
  • The bidomain model identified nonlinearities in the inward rectifier potassium current as the cause of this asymmetry.

Conclusions:

  • The study confirms the presence of VEPs at all stimulus strengths, including subthreshold diastolic stimuli.
  • Active ion channel kinetics play a crucial role in modulating transmembrane polarization patterns, refining predictions from linear bidomain models.