Cardiovascular Research Institute

You are here

Applications of Dynamic Clamp to Cardiac Arrhythmia Research: Role in Drug Target Discovery and Safety Pharmacology Testing.

TitleApplications of Dynamic Clamp to Cardiac Arrhythmia Research: Role in Drug Target Discovery and Safety Pharmacology Testing.
Publication TypeJournal Article
Year of Publication2017
AuthorsOrtega, FA, Grandi, E, Krogh-Madsen, T, Christini, DJ
JournalFront Physiol
Volume8
Pagination1099
Date Published2017
ISSN1664-042X
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.

DOI10.3389/fphys.2017.01099
Alternate JournalFront Physiol
PubMed ID29354069
PubMed Central IDPMC5758594
Grant ListR01 HL131517 / HL / NHLBI NIH HHS / United States
U01 HL136297 / HL / NHLBI NIH HHS / United States