Selective inhibition of sodium-calcium exchanger by SEA-0400 decreases early and delayed afterdepolarization in canine heart

Zsolt A. Nagy, L. Virág, A. Tóth, P. Biliczki, K. Acsai, Tamás Bányász, P. Nánási, J. Papp, A. Varró

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Abstract

The sodium-calcium exchanger (NCX) was considered to play an important role in arrhythmogenesis under certain conditions such as heart failure or calcium overload. In the present study, the effect of SEA-0400, a selective inhibitor of the NCX, was investigated on early and delayed afterdepolarizations in canine ventricular papillary muscles and Purkinje fibres by applying conventional microelectrode techniques at 37°C. The amplitude of both early and delayed afterdepolarizations was markedly decreased by 1 μM SEA-0400 from 26.6 ± 2.5 to 14.8 ± 1.8 mV (n = 9, P <0.05) and from 12.5 ± 1.7 to 5.9 ± 1.4 mV (n = 3, P <0.05), respectively. In enzymatically isolated canine ventricular myocytes, SEA-0400 did not change significantly the L-type calcium current and the intracellular calcium transient, studied using the whole-cell configuration of the patch-clamp technique and Fura-2 ratiometric fluorometry. It is concluded that, through the reduction of calcium overload, specific inhibition of the NCX current by SEA-0400 may abolish triggered arrhythmias.

Original languageEnglish
Pages (from-to)827-831
Number of pages5
JournalBritish Journal of Pharmacology
Volume143
Issue number7
DOIs
Publication statusPublished - Dec 2004

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Sodium-Calcium Exchanger
Canidae
Calcium
Purkinje Fibers
Fluorometry
Papillary Muscles
Fura-2
Microelectrodes
Patch-Clamp Techniques
Muscle Cells
Cardiac Arrhythmias
Heart Failure
SEA 0400

Keywords

  • Calcium transient
  • Early and delayed afterdepolarizations
  • L-type calcium current
  • Papillary muscle
  • Purkinje fibres
  • SEA-0400
  • Sodium/calcium exchanger

ASJC Scopus subject areas

  • Pharmacology

Cite this

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title = "Selective inhibition of sodium-calcium exchanger by SEA-0400 decreases early and delayed afterdepolarization in canine heart",
abstract = "The sodium-calcium exchanger (NCX) was considered to play an important role in arrhythmogenesis under certain conditions such as heart failure or calcium overload. In the present study, the effect of SEA-0400, a selective inhibitor of the NCX, was investigated on early and delayed afterdepolarizations in canine ventricular papillary muscles and Purkinje fibres by applying conventional microelectrode techniques at 37°C. The amplitude of both early and delayed afterdepolarizations was markedly decreased by 1 μM SEA-0400 from 26.6 ± 2.5 to 14.8 ± 1.8 mV (n = 9, P <0.05) and from 12.5 ± 1.7 to 5.9 ± 1.4 mV (n = 3, P <0.05), respectively. In enzymatically isolated canine ventricular myocytes, SEA-0400 did not change significantly the L-type calcium current and the intracellular calcium transient, studied using the whole-cell configuration of the patch-clamp technique and Fura-2 ratiometric fluorometry. It is concluded that, through the reduction of calcium overload, specific inhibition of the NCX current by SEA-0400 may abolish triggered arrhythmias.",
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author = "Nagy, {Zsolt A.} and L. Vir{\'a}g and A. T{\'o}th and P. Biliczki and K. Acsai and Tam{\'a}s B{\'a}ny{\'a}sz and P. N{\'a}n{\'a}si and J. Papp and A. Varr{\'o}",
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T1 - Selective inhibition of sodium-calcium exchanger by SEA-0400 decreases early and delayed afterdepolarization in canine heart

AU - Nagy, Zsolt A.

AU - Virág, L.

AU - Tóth, A.

AU - Biliczki, P.

AU - Acsai, K.

AU - Bányász, Tamás

AU - Nánási, P.

AU - Papp, J.

AU - Varró, A.

PY - 2004/12

Y1 - 2004/12

N2 - The sodium-calcium exchanger (NCX) was considered to play an important role in arrhythmogenesis under certain conditions such as heart failure or calcium overload. In the present study, the effect of SEA-0400, a selective inhibitor of the NCX, was investigated on early and delayed afterdepolarizations in canine ventricular papillary muscles and Purkinje fibres by applying conventional microelectrode techniques at 37°C. The amplitude of both early and delayed afterdepolarizations was markedly decreased by 1 μM SEA-0400 from 26.6 ± 2.5 to 14.8 ± 1.8 mV (n = 9, P <0.05) and from 12.5 ± 1.7 to 5.9 ± 1.4 mV (n = 3, P <0.05), respectively. In enzymatically isolated canine ventricular myocytes, SEA-0400 did not change significantly the L-type calcium current and the intracellular calcium transient, studied using the whole-cell configuration of the patch-clamp technique and Fura-2 ratiometric fluorometry. It is concluded that, through the reduction of calcium overload, specific inhibition of the NCX current by SEA-0400 may abolish triggered arrhythmias.

AB - The sodium-calcium exchanger (NCX) was considered to play an important role in arrhythmogenesis under certain conditions such as heart failure or calcium overload. In the present study, the effect of SEA-0400, a selective inhibitor of the NCX, was investigated on early and delayed afterdepolarizations in canine ventricular papillary muscles and Purkinje fibres by applying conventional microelectrode techniques at 37°C. The amplitude of both early and delayed afterdepolarizations was markedly decreased by 1 μM SEA-0400 from 26.6 ± 2.5 to 14.8 ± 1.8 mV (n = 9, P <0.05) and from 12.5 ± 1.7 to 5.9 ± 1.4 mV (n = 3, P <0.05), respectively. In enzymatically isolated canine ventricular myocytes, SEA-0400 did not change significantly the L-type calcium current and the intracellular calcium transient, studied using the whole-cell configuration of the patch-clamp technique and Fura-2 ratiometric fluorometry. It is concluded that, through the reduction of calcium overload, specific inhibition of the NCX current by SEA-0400 may abolish triggered arrhythmias.

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