Limited role of Ca2+-activated Cl- current in early afterdepolarisations

• Published in: Netherlands heart journal Vol. 10; no. 12; pp. 506 - 511
• Main Authors: Verkerk, A O, Tan, H L, Baartscheer, T, Ravesloot, J H
• Format: Journal Article
• Language: English
• Published: 01-12-2002
• Subjects: Original
• ISSN: 1568-5888

OBJECTIVESThe proarrhythmic, early afterdepolarisations during phase two of the action potential (phase-2 EADs) are associated with secondary Ca2+ release from the sarcoplasmic reticulum. This makes it probable that the Ca2+-activated Cl- current (ICl(Ca)) may contribute to phase-2 EADs. Activation of ICl(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. METHODSThe contribution of ICl(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. RESULTSThe ICl(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 ICl(Ca) is present in all myocytes. However, DIDS had no effect on phase-2 EAD characteristics. CONCLUSIONIn sheep ventricular myocytes, ICl(Ca) contributes to phase-1 repolarisation of the action potential, but plays a limited role in phase-2 EADs.