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Updated: Aug 30, 2026

Isolation of Human Atrial Myocytes for Simultaneous Measurements of Ca2+ Transients and Membrane Currents
Published on: July 3, 2013
Role of Ca2+-activated Cl- current during proarrhythmic early afterdepolarizations in sheep and human ventricular
A O Verkerk1, H L Tan, J H Kirkels
1Department of Physiology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
Objectives:
The proarrhythmic early afterdepolarizations (EADs) during phase-2 of the cardiac action potential (phase-2 EADs) are associated with secondary Ca2+-release of the sarcoplasmic reticulum. This makes it probable that the Ca2+-activated Cl- current [ICl(Ca)] is present during phase-2 EADs. Activation of ICl(Ca) during phase-2 of the action potential will result in an outwardly directed, repolarizing current and may thus be expected to prevent excessive depolarization of phase-2 EADs. The present study was designed to test this hypothesis.
Methods And Results:
The contribution of ICl(Ca) during phase-2 EADs was studied in enzymatically isolated sheep and human ventricular myocytes using the patch-clamp methodology. EADs were induced by a combination of a low stimulus frequency (0.5 Hz) and exposure to 1 microm noradrenaline. In sheep myocytes, the ICl(Ca) blocker 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid (DIDS, 0.5 mm) abolished phase-1 repolarization of the action potential in all myocytes tested. This indicates that ICl(Ca) is present in all sheep myocytes. However, DIDS had no effect on phase-2 EAD characteristics. In human myocytes, DIDS neither affected phase-1 repolarization nor phase-2 EAD characteristics.
Conclusion:
In sheep ventricular myocytes, but not in human ventricular myocytes, ICl(Ca) contributes to phase-1 repolarization of the action potential. In both sheep and human myocytes, ICl(Ca) plays a limited role during phase-2 EADs.
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