title: Role of action potential configuration and the contribution of C²⁺a and K⁺ currents to isoprenaline-induced changes in canine ventricular cells.
abstract: OBJECTIVE
  Although isoprenaline (ISO) is known to activate several ion currents in mammalian myocardium, little is known about the role of action potential morphology in the ISO-induced changes in ion currents. Therefore, the effects of ISO on action potential configuration, L-type Ca²⁺ current (I(Ca)), slow delayed rectifier K⁺ current (I(Ks)) and fast delayed rectifier K⁺ current (I(Kr)) were studied and compared in a frequency-dependent manner using canine isolated ventricular myocytes from various transmural locations.
  
  
  METHODS
  Action potentials were recorded with conventional sharp microelectrodes; ion currents were measured using conventional and action potential voltage clamp techniques.
  
  
  RESULTS
  In myocytes displaying a spike-and-dome action potential configuration (epicardial and midmyocardial cells), ISO caused reversible shortening of action potentials accompanied by elevation of the plateau. ISO-induced action potential shortening was absent in endocardial cells and in myocytes pretreated with 4-aminopyridine. Application of the I(Kr) blocker E-4031 failed to modify the ISO effect, while action potentials were lengthened by ISO in the presence of the I(Ks) blocker HMR-1556. Both action potential shortening and elevation of the plateau were prevented by pretreatment with the I(Ca) blocker nisoldipine. Action potential voltage clamp experiments revealed a prominent slowly inactivating I(Ca) followed by a rise in I(Ks) , both currents increased with increasing the cycle length.
  
  
  CONCLUSIONS
  The effect of ISO in canine ventricular cells depends critically on action potential configuration, and the ISO-induced activation of I(Ks) - but not I(Kr) - may be responsible for the observed shortening of action potentials.
authors.affiliation: Department of Physiology, University of Debrecen, Hungary.
authors.forename: N
authors.initials: N
authors.lastname: Szentandrássy
authors.forename: V
authors.initials: V
authors.lastname: Farkas
authors.forename: L
authors.initials: L
authors.lastname: Bárándi
authors.forename: B
authors.initials: B
authors.lastname: Hegyi
authors.forename: F
authors.initials: F
authors.lastname: Ruzsnavszky
authors.forename: B
authors.initials: B
authors.lastname: Horváth
authors.forename: T
authors.initials: T
authors.lastname: Bányász
authors.forename: J
authors.initials: J
authors.lastname: Magyar
authors.forename: I
authors.initials: I
authors.lastname: Márton
authors.forename: P P
authors.initials: PP
authors.lastname: Nánási
mesh_terms: D000200:Action Potentials / Q000187:drug effects*; D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000818:Animals; D020746:Calcium Channels, L-Type / Q000378:metabolism; D002839:Chromans / Q000494:pharmacology; D051668:Delayed Rectifier Potassium Channels / Q000378:metabolism*; D004285:Dogs; D005260:Female; D007545:Isoproterenol / Q000494:pharmacology*; D008297:Male; D032383:Myocytes, Cardiac / Q000187:drug effects* / Q000378:metabolism; D015737:Nisoldipine / Q000494:pharmacology; D018408:Patch-Clamp Techniques; D010880:Piperidines / Q000494:pharmacology; D011725:Pyridines / Q000494:pharmacology; D013449:Sulfonamides / Q000494:pharmacology
chemical_list: D000318:Adrenergic beta-Agonists; D020746:Calcium Channels, L-Type; D002839:Chromans; D051668:Delayed Rectifier Potassium Channels; C420023:HMR 1556; D010880:Piperidines; D011725:Pyridines; D013449:Sulfonamides; C063968:E 4031; D015737:Nisoldipine; D007545:Isoproterenol