Applications of dynamic clamp to cardiac arrhythmia research: Role in drug target discovery and safety pharmacology testing

Francis A. Ortega, Eleonora Grandi, Trine Krogh-Madsen, David J. Christini

Research output: Contribution to journalShort surveypeer-review

12 Scopus citations

Abstract

Dynamic clamp, a hybrid-computational-experimental technique that has been used to elucidate ionic mechanisms underlying cardiac electrophysiology, is emerging as a promising tool in the discovery of potential anti-arrhythmic targets and in pharmacological safety testing. Through the injection of computationally simulated conductances into isolated cardiomyocytes in a real-time continuous loop, dynamic clamp has greatly expanded the capabilities of patch clamp outside traditional static voltage and current protocols. Recent applications include fine manipulation of injected artificial conductances to identify promising drug targets in the prevention of arrhythmia and the direct testing of model-based hypotheses. Furthermore, dynamic clamp has been used to enhance existing experimental models by addressing their intrinsic limitations, which increased predictive power in identifying pro-arrhythmic pharmacological compounds. Here, we review the recent advances of the dynamic clamp technique in cardiac electrophysiology with a focus on its future role in the development of safety testing and discovery of anti-arrhythmic drugs.

Original languageEnglish (US)
Article number1099
JournalFrontiers in Physiology
Volume8
Issue numberJAN
DOIs
StatePublished - Jan 4 2018

Keywords

  • Antiarrhythmic drugs
  • Arrhythmia mechanisms
  • Cardiac electrophysiology
  • Cardiac modeling
  • Dynamic clamp
  • Pharmacology & drug discovery

ASJC Scopus subject areas

  • Physiology
  • Physiology (medical)

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