TY - JOUR
T1 - Applications of dynamic clamp to cardiac arrhythmia research
T2 - Role in drug target discovery and safety pharmacology testing
AU - Ortega, Francis A.
AU - Grandi, Eleonora
AU - Krogh-Madsen, Trine
AU - Christini, David J.
PY - 2018/1/4
Y1 - 2018/1/4
N2 - 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.
AB - 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.
KW - Antiarrhythmic drugs
KW - Arrhythmia mechanisms
KW - Cardiac electrophysiology
KW - Cardiac modeling
KW - Dynamic clamp
KW - Pharmacology & drug discovery
UR - http://www.scopus.com/inward/record.url?scp=85040019820&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85040019820&partnerID=8YFLogxK
U2 - 10.3389/fphys.2017.01099
DO - 10.3389/fphys.2017.01099
M3 - Short survey
AN - SCOPUS:85040019820
VL - 8
JO - Frontiers in Physiology
JF - Frontiers in Physiology
SN - 1664-042X
IS - JAN
M1 - 1099
ER -