Limited role of Ca 2+ -activated Cl - current in early afterdepolarisations.

Objectives: The proarrhythmic, early afterdepolarisations during phase two of the action potential (phase-2 EADs) are associated with secondary Ca ²⁺ release from the sarcoplasmic reticulum. This makes it probable that the Ca ²⁺ -activated Cl ^- current (I _Cl(Ca) ) may contribute to phase-2 EADs. Activation of I _Cl(Ca) during phase two of the action potential will result in a repolarising current and may thus be expected to prevent excessive depolarisation of phase-2 EADs. The present study was designed to test this hypothesis.
Methods: The contribution of I _Cl(Ca) during phase-2 EADs was studied in enzymatically isolated sheep ventricular myocytes using the patch-clamp methodology. EADs were induced at a stimulus frequency of 0.5 Hz by exposure of the myocytes to 1 μM noradrenaline.
Results: The I _Cl(Ca) blocker 4,4'-diisothiocyanostilbene-2,2'-disulphonic acid (DIDS, 0.5 mM) abolished phase-1 repolarisation of the action potential in all myocytes tested. This indicates that I _Cl(Ca) is present in all myocytes. However, DIDS had no effect on phase-2 EAD characteristics.
Conclusion: In sheep ventricular myocytes, I _Cl(Ca) contributes to phase-1 repolarisation of the action potential, but plays a limited role in phase-2 EADs.