OBJECTIVES: The 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. METHODS: The 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. RESULTS: The 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. CONCLUSION: In sheep ventricular myocytes, ICl(Ca) contributes to phase-1 repolarisation of the action potential, but plays a limited role in phase-2 EADs.
OBJECTIVES: The 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. METHODS: The 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. RESULTS: The 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. CONCLUSION: In sheep ventricular myocytes, ICl(Ca) contributes to phase-1 repolarisation of the action potential, but plays a limited role in phase-2 EADs.
Authors: S M Kamel; C J M van Opbergen; C D Koopman; A O Verkerk; B J D Boukens; B de Jonge; Y L Onderwater; E van Alebeek; S Chocron; C Polidoro Pontalti; W J Weuring; M A Vos; T P de Boer; T A B van Veen; J Bakkers Journal: Nat Commun Date: 2021-12-09 Impact factor: 14.919