title: Cl-current blockade reduces triggered activity based on delayed afterdepolarisations.
abstract: OBJECTIVE
  Increasing evidence suggests that a Ca2+-activated Cl-current (ICl(Ca)) contributes to the transient inward current (Iti), the current responsible for proarrhythmic delayed after-depolarisations (DADs). Because the equilibrium potential for Cl-ions (ECl) in myocytes is around - 50 mV, activation of the ICl(Ca)results in an inward depolarising current at resting membrane potential and ICl(Ca)may thus be responsible for a part of the depolarisation during a DAD. In this study, we investigated the ionic nature of Itiand the effects of Cl-current blockade on DADs.
  
  
  RESULTS
  The ionic mechanisms of Itiand underlying DADs were studied in sheep ventricular myocytes using the patch-clamp methodology. The DADs were induced in the myocytes by exposure to 1 μM noradrenaline and the Itiwere elicited by repetitive depolarisations from -93 mV to +37 mV in the presence of the drug. The current-voltage relation of Itireversed in sign around -20 mV. The outward Itiwas completely blocked by the anion current blocker 4,4'-diisothiocyanatostilbene-2,2'-disulphonic acid (DIDS), whereas the inward Itiwas only slightly affected. The DIDS-sensitive component of Itiwas outwardly rectifying with a reversal potential close to ECl. The DIDS-insensitive component of Itiwas abolished by blockade of the Na+-Ca2+exchanger by substitution of extracellular Na+by equimolar Li+. Interestingly, DIDS reduced the DAD amplitude and triggered activity based on DADs.
  
  
  CONCLUSIONS
  In sheep ventricular myocytes, Iticonsists of two ionic mechanisms: a Cl-current and a Na+-Ca2+exchange current. Blockade of the Cl-current may be potentially antiarrhythmic by lowering DAD amplitude and triggered activity based on DADs.
authors.forename: A O
authors.initials: AO
authors.lastname: Verkerk
authors.forename: M W
authors.initials: MW
authors.lastname: Veldkamp
authors.forename: A C G
authors.initials: AC
authors.lastname: van Ginneken
keywords: afterdepolarisation