Document Detail

Analysis of the contribution of I(to) to repolarization in canine ventricular myocardium.
MedLine Citation:
PMID:  21410683     Owner:  NLM     Status:  MEDLINE    
BACKGROUND AND PURPOSE: The contribution of the transient outward potassium current (I(to)) to ventricular repolarization is controversial as it depends on the experimental conditions, the region of myocardium and the species studied. The aim of the present study was therefore to characterize I(to) and estimate its contribution to repolarization reserve in canine ventricular myocardium.
EXPERIMENTAL APPROACH: Ion currents were recorded using conventional whole-cell voltage clamp and action potential voltage clamp techniques in canine isolated ventricular cells. Action potentials were recorded from canine ventricular preparations using microelectrodes. The contribution of I(to) to repolarization was studied using 100 µM chromanol 293B in the presence of 0.5 µM HMR 1556, which fully blocks I(Ks).
KEY RESULTS: The high concentration of chromanol 293B used effectively suppressed I(to) without affecting other repolarizing K(+) currents (I(K1), I(Kr), I(p)). Action potential clamp experiments revealed a slowly inactivating and a 'late' chromanol-sensitive current component occurring during the action potential plateau. Action potentials were significantly lengthened by chromanol 293B in the presence of HMR 1556. This lengthening effect induced by I(to) inhibition was found to be reverse rate-dependent. It was significantly augmented after additional attenuation of repolarization reserve by 0.1 µM dofetilide and this caused the occurrence of early afterdepolarizations. The results were confirmed by computer simulation.
CONCLUSIONS AND IMPLICATIONS: The results indicate that I(to) is involved in regulating repolarization in canine ventricular myocardium and that it contributes significantly to the repolarization reserve. Therefore, blockade of I(to) may enhance pro-arrhythmic risk.
L Virág; N Jost; R Papp; I Koncz; A Kristóf; Z Kohajda; G Harmati; B Carbonell-Pascual; J M Ferrero; J G Papp; P P Nánási; A Varró
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  British journal of pharmacology     Volume:  164     ISSN:  1476-5381     ISO Abbreviation:  Br. J. Pharmacol.     Publication Date:  2011 Sep 
Date Detail:
Created Date:  2011-08-08     Completed Date:  2012-02-02     Revised Date:  2013-06-30    
Medline Journal Info:
Nlm Unique ID:  7502536     Medline TA:  Br J Pharmacol     Country:  England    
Other Details:
Languages:  eng     Pagination:  93-105     Citation Subset:  IM    
Copyright Information:
© 2011 The Authors. British Journal of Pharmacology © 2011 The British Pharmacological Society.
Department of Pharmacology and Pharmacotherapy, University of Szeged, Szeged, Hungary.
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MeSH Terms
Action Potentials / drug effects
Chromans / pharmacology
Heart Conduction System / metabolism*
Heart Ventricles / drug effects,  metabolism
Myocardium / cytology,  metabolism*
Myocytes, Cardiac / drug effects,  metabolism*
Patch-Clamp Techniques
Phenethylamines / pharmacology
Potassium Channel Blockers / pharmacology
Potassium Channels / metabolism*
Sulfonamides / pharmacology
Ventricular Function / drug effects
Reg. No./Substance:
0/Chromans; 0/HMR 1556; 0/Phenethylamines; 0/Potassium Channel Blockers; 0/Potassium Channels; 0/Sulfonamides; 115256-11-6/dofetilide; 163163-23-3/6-cyano-4-(N-ethylsulfonyl-N-methylamino)-3-hydroxy-2,2-dimethylchromane

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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