Cytosolic calcium changes affect the incidence of early afterdepolarizations in canine ventricular myocytes

Balázs Horváth, Bence Hegyi, Kornél Kistamás, Krisztina Váczi, Tamás Bányász, J. Magyar, N. Szentandrássy, P. Nánási

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

This study was designed to investigate the influence of cytosolic Ca2+ levels ([Ca2+]i) on action potential duration (APD) and on the incidence of early afterdepolarizations (EADs) in canine ventricular cardiomyocytes. Action potentials (AP) of isolated cells were recorded using conventional sharp microelectrodes, and the concomitant [Ca2+]i was monitored with the fluorescent dye Fura-2. EADs were evoked at a 0.2 Hz pacing rate by inhibiting the rapid delayed rectifier K+ current with dofetilide, by activating the late sodium current with veratridine, or by activating the L-type calcium current with BAY K8644. These interventions progressively prolonged the AP and resulted in initiation of EADs. Reducing [Ca2+]i by application of the cell-permeant Ca2+ chelator BAPTA-AM lengthened the AP at 1.0 Hz if it was applied alone, in the presence of veratridine, or in the presence of BAY K8644. However, BAPTA-AM shortened the AP if the cells were pretreated with dofetilide. The incidence of the evoked EADs was strongly reduced by BAPTA-AM in dofetilide, moderately reduced in veratridine, whereas EAD incidence was increased by BAPTA-AM in the presence of BAY K8644. Based on these experimental data, changes in [Ca2+]i have marked effects on APD as well as on the incidence of EADs; however, the underlying mechanisms may be different, depending on the mechanism of EAD generation. As a consequence, reduction of [Ca2+]i may eliminate EADs under some, but not all, experimental conditions.

Original languageEnglish
Pages (from-to)527-534
Number of pages8
JournalCanadian Journal of Physiology and Pharmacology
Volume93
Issue number7
DOIs
Publication statusPublished - Mar 11 2015

Fingerprint

Muscle Cells
Action Potentials
Canidae
Veratridine
Calcium
Incidence
Fura-2
Microelectrodes
Chelating Agents
Fluorescent Dyes
Cardiac Myocytes
Sodium
1,2-bis(2-aminophenoxy)ethane N,N,N',N'-tetraacetic acid acetoxymethyl ester
dofetilide

Keywords

  • Action potential duration
  • Arrhythmogenesis
  • Ca chelators
  • Canine myocytes
  • Early afterdepolarizations
  • Electrophysiology
  • Fluorescent Ca indicator dyes
  • Intracellular Ca levels

ASJC Scopus subject areas

  • Physiology
  • Physiology (medical)
  • Pharmacology

Cite this

Cytosolic calcium changes affect the incidence of early afterdepolarizations in canine ventricular myocytes. / Horváth, Balázs; Hegyi, Bence; Kistamás, Kornél; Váczi, Krisztina; Bányász, Tamás; Magyar, J.; Szentandrássy, N.; Nánási, P.

In: Canadian Journal of Physiology and Pharmacology, Vol. 93, No. 7, 11.03.2015, p. 527-534.

Research output: Contribution to journalArticle

Horváth, Balázs ; Hegyi, Bence ; Kistamás, Kornél ; Váczi, Krisztina ; Bányász, Tamás ; Magyar, J. ; Szentandrássy, N. ; Nánási, P. / Cytosolic calcium changes affect the incidence of early afterdepolarizations in canine ventricular myocytes. In: Canadian Journal of Physiology and Pharmacology. 2015 ; Vol. 93, No. 7. pp. 527-534.
@article{32d988cd452749b0b80f50381a6d83b0,
title = "Cytosolic calcium changes affect the incidence of early afterdepolarizations in canine ventricular myocytes",
abstract = "This study was designed to investigate the influence of cytosolic Ca2+ levels ([Ca2+]i) on action potential duration (APD) and on the incidence of early afterdepolarizations (EADs) in canine ventricular cardiomyocytes. Action potentials (AP) of isolated cells were recorded using conventional sharp microelectrodes, and the concomitant [Ca2+]i was monitored with the fluorescent dye Fura-2. EADs were evoked at a 0.2 Hz pacing rate by inhibiting the rapid delayed rectifier K+ current with dofetilide, by activating the late sodium current with veratridine, or by activating the L-type calcium current with BAY K8644. These interventions progressively prolonged the AP and resulted in initiation of EADs. Reducing [Ca2+]i by application of the cell-permeant Ca2+ chelator BAPTA-AM lengthened the AP at 1.0 Hz if it was applied alone, in the presence of veratridine, or in the presence of BAY K8644. However, BAPTA-AM shortened the AP if the cells were pretreated with dofetilide. The incidence of the evoked EADs was strongly reduced by BAPTA-AM in dofetilide, moderately reduced in veratridine, whereas EAD incidence was increased by BAPTA-AM in the presence of BAY K8644. Based on these experimental data, changes in [Ca2+]i have marked effects on APD as well as on the incidence of EADs; however, the underlying mechanisms may be different, depending on the mechanism of EAD generation. As a consequence, reduction of [Ca2+]i may eliminate EADs under some, but not all, experimental conditions.",
keywords = "Action potential duration, Arrhythmogenesis, Ca chelators, Canine myocytes, Early afterdepolarizations, Electrophysiology, Fluorescent Ca indicator dyes, Intracellular Ca levels",
author = "Bal{\'a}zs Horv{\'a}th and Bence Hegyi and Korn{\'e}l Kistam{\'a}s and Krisztina V{\'a}czi and Tam{\'a}s B{\'a}ny{\'a}sz and J. Magyar and N. Szentandr{\'a}ssy and P. N{\'a}n{\'a}si",
year = "2015",
month = "3",
day = "11",
doi = "10.1139/cjpp-2014-0511",
language = "English",
volume = "93",
pages = "527--534",
journal = "Canadian Journal of Physiology and Pharmacology",
issn = "0008-4212",
publisher = "National Research Council of Canada",
number = "7",

}

TY - JOUR

T1 - Cytosolic calcium changes affect the incidence of early afterdepolarizations in canine ventricular myocytes

AU - Horváth, Balázs

AU - Hegyi, Bence

AU - Kistamás, Kornél

AU - Váczi, Krisztina

AU - Bányász, Tamás

AU - Magyar, J.

AU - Szentandrássy, N.

AU - Nánási, P.

PY - 2015/3/11

Y1 - 2015/3/11

N2 - This study was designed to investigate the influence of cytosolic Ca2+ levels ([Ca2+]i) on action potential duration (APD) and on the incidence of early afterdepolarizations (EADs) in canine ventricular cardiomyocytes. Action potentials (AP) of isolated cells were recorded using conventional sharp microelectrodes, and the concomitant [Ca2+]i was monitored with the fluorescent dye Fura-2. EADs were evoked at a 0.2 Hz pacing rate by inhibiting the rapid delayed rectifier K+ current with dofetilide, by activating the late sodium current with veratridine, or by activating the L-type calcium current with BAY K8644. These interventions progressively prolonged the AP and resulted in initiation of EADs. Reducing [Ca2+]i by application of the cell-permeant Ca2+ chelator BAPTA-AM lengthened the AP at 1.0 Hz if it was applied alone, in the presence of veratridine, or in the presence of BAY K8644. However, BAPTA-AM shortened the AP if the cells were pretreated with dofetilide. The incidence of the evoked EADs was strongly reduced by BAPTA-AM in dofetilide, moderately reduced in veratridine, whereas EAD incidence was increased by BAPTA-AM in the presence of BAY K8644. Based on these experimental data, changes in [Ca2+]i have marked effects on APD as well as on the incidence of EADs; however, the underlying mechanisms may be different, depending on the mechanism of EAD generation. As a consequence, reduction of [Ca2+]i may eliminate EADs under some, but not all, experimental conditions.

AB - This study was designed to investigate the influence of cytosolic Ca2+ levels ([Ca2+]i) on action potential duration (APD) and on the incidence of early afterdepolarizations (EADs) in canine ventricular cardiomyocytes. Action potentials (AP) of isolated cells were recorded using conventional sharp microelectrodes, and the concomitant [Ca2+]i was monitored with the fluorescent dye Fura-2. EADs were evoked at a 0.2 Hz pacing rate by inhibiting the rapid delayed rectifier K+ current with dofetilide, by activating the late sodium current with veratridine, or by activating the L-type calcium current with BAY K8644. These interventions progressively prolonged the AP and resulted in initiation of EADs. Reducing [Ca2+]i by application of the cell-permeant Ca2+ chelator BAPTA-AM lengthened the AP at 1.0 Hz if it was applied alone, in the presence of veratridine, or in the presence of BAY K8644. However, BAPTA-AM shortened the AP if the cells were pretreated with dofetilide. The incidence of the evoked EADs was strongly reduced by BAPTA-AM in dofetilide, moderately reduced in veratridine, whereas EAD incidence was increased by BAPTA-AM in the presence of BAY K8644. Based on these experimental data, changes in [Ca2+]i have marked effects on APD as well as on the incidence of EADs; however, the underlying mechanisms may be different, depending on the mechanism of EAD generation. As a consequence, reduction of [Ca2+]i may eliminate EADs under some, but not all, experimental conditions.

KW - Action potential duration

KW - Arrhythmogenesis

KW - Ca chelators

KW - Canine myocytes

KW - Early afterdepolarizations

KW - Electrophysiology

KW - Fluorescent Ca indicator dyes

KW - Intracellular Ca levels

UR - http://www.scopus.com/inward/record.url?scp=84943535925&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84943535925&partnerID=8YFLogxK

U2 - 10.1139/cjpp-2014-0511

DO - 10.1139/cjpp-2014-0511

M3 - Article

VL - 93

SP - 527

EP - 534

JO - Canadian Journal of Physiology and Pharmacology

JF - Canadian Journal of Physiology and Pharmacology

SN - 0008-4212

IS - 7

ER -