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Isolation of Human Atrial Myocytes for Simultaneous Measurements of Ca2+ Transients and Membrane Currents
Published on: July 3, 2013
L-type calcium current reactivation contributes to arrhythmogenesis associated with action potential triangulation
Donglin Guo1, Xiaojing Zhao, Ying Wu
1Main Line Health Heart Center, Wynnewood, Pennsylvania 19096, USA. guod@mlhs.org
Cardiac action potential (AP) shape influences drug-induced arrhythmias. AP triangulation in rabbits accelerates calcium channel recovery, increasing torsade de pointes risk.
Area of Science:
- Cardiovascular Physiology
- Electrophysiology
- Pharmacology
Background:
- Mammalian cardiac action potential (AP) morphology impacts susceptibility to drug-induced early afterdepolarizations (EADs).
- AP triangulation is a known predictor of drug-induced torsade de pointes (TdP).
Purpose of the Study:
- To investigate the electrophysiological basis of AP triangulation in mammalian ventricular myocytes.
- To determine the effect of AP shape on calcium channel (I(Ca-L)) recovery from inactivation.
Main Methods:
- Recorded cardiac action potentials in guinea pig and rabbit ventricular myocytes using microelectrode techniques.
- Measured I(Ca-L) currents using patch-clamp electrophysiology.
- Employed AP voltage-clamp protocols to simulate different AP waveforms.
Main Results:
- Rabbit myocytes exhibited triangular APs, while guinea pig myocytes showed square APs.
- Dofetilide-induced EADs were observed only in rabbit myocytes.
- AP triangulation significantly accelerated I(Ca-L) recovery from inactivation in both species.
Conclusions:
- In rabbit ventricular myocardium, AP triangulation accelerates I(Ca-L) channel recovery.
- This accelerated recovery leads to repolarization instability, initiating TdP.
- AP shape is a critical determinant of arrhythmogenic potential.
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