Analysis of the contribution of I to to repolarization in canine ventricular myocardium

L. Virág, N. Jost, R. Papp, I. Koncz, A. Kristóf, Z. Kohajda, G. Harmati, B. Carbonell-Pascual, J. M. Ferrero, J. Papp, P. Nánási, A. Varró

Research output: Contribution to journalArticle

14 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)93-105
Number of pages13
JournalBritish Journal of Pharmacology
Volume164
Issue number1
DOIs
Publication statusPublished - Sep 2011

Fingerprint

Action Potentials
Canidae
Myocardium
Microelectrodes
Patch-Clamp Techniques
Computer Simulation
Potassium
Ions
6-cyano-4-(N-ethylsulfonyl-N-methylamino)-3-hydroxy-2,2-dimethylchromane
HMR 1556

Keywords

  • action potential duration
  • arrhythmia
  • cardiac ventricular muscle
  • repolarization reserve
  • transient outward current

ASJC Scopus subject areas

  • Pharmacology

Cite this

Analysis of the contribution of I to to repolarization in canine ventricular myocardium. / Virág, L.; Jost, N.; Papp, R.; Koncz, I.; Kristóf, A.; Kohajda, Z.; Harmati, G.; Carbonell-Pascual, B.; Ferrero, J. M.; Papp, J.; Nánási, P.; Varró, A.

In: British Journal of Pharmacology, Vol. 164, No. 1, 09.2011, p. 93-105.

Research output: Contribution to journalArticle

Virág, L. ; Jost, N. ; Papp, R. ; Koncz, I. ; Kristóf, A. ; Kohajda, Z. ; Harmati, G. ; Carbonell-Pascual, B. ; Ferrero, J. M. ; Papp, J. ; Nánási, P. ; Varró, A. / Analysis of the contribution of I to to repolarization in canine ventricular myocardium. In: British Journal of Pharmacology. 2011 ; Vol. 164, No. 1. pp. 93-105.
@article{07c338b6a40b47a78d30eb42c9d3270c,
title = "Analysis of the contribution of I to to repolarization in canine ventricular myocardium",
abstract = "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.",
keywords = "action potential duration, arrhythmia, cardiac ventricular muscle, repolarization reserve, transient outward current",
author = "L. Vir{\'a}g and N. Jost and R. Papp and I. Koncz and A. Krist{\'o}f and Z. Kohajda and G. Harmati and B. Carbonell-Pascual and Ferrero, {J. M.} and J. Papp and P. N{\'a}n{\'a}si and A. Varr{\'o}",
year = "2011",
month = "9",
doi = "10.1111/j.1476-5381.2011.01331.x",
language = "English",
volume = "164",
pages = "93--105",
journal = "British Journal of Pharmacology",
issn = "0007-1188",
publisher = "Wiley-Blackwell",
number = "1",

}

TY - JOUR

T1 - Analysis of the contribution of I to to repolarization in canine ventricular myocardium

AU - Virág, L.

AU - Jost, N.

AU - Papp, R.

AU - Koncz, I.

AU - Kristóf, A.

AU - Kohajda, Z.

AU - Harmati, G.

AU - Carbonell-Pascual, B.

AU - Ferrero, J. M.

AU - Papp, J.

AU - Nánási, P.

AU - Varró, A.

PY - 2011/9

Y1 - 2011/9

N2 - 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.

AB - 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.

KW - action potential duration

KW - arrhythmia

KW - cardiac ventricular muscle

KW - repolarization reserve

KW - transient outward current

UR - http://www.scopus.com/inward/record.url?scp=79961245166&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=79961245166&partnerID=8YFLogxK

U2 - 10.1111/j.1476-5381.2011.01331.x

DO - 10.1111/j.1476-5381.2011.01331.x

M3 - Article

C2 - 21410683

AN - SCOPUS:79961245166

VL - 164

SP - 93

EP - 105

JO - British Journal of Pharmacology

JF - British Journal of Pharmacology

SN - 0007-1188

IS - 1

ER -