Asynchronous activation of calcium and potassium currents by isoproterenol in canine ventricular myocytes

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

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

Adrenergic activation of L-type Ca2+ and various K+ currents is a crucial mechanism of cardiac adaptation; however, it may carry a substantial proarrhythmic risk as well. The aim of the present work was to study the timing of activation of Ca2+ and K+ currents in isolated canine ventricular cells in response to exposure to isoproterenol (ISO). Whole cell configuration of the patch-clamp technique in either conventional voltage clamp or action potential voltage clamp modes were used to monitor I Ca, I Ks, and I Kr, while action potentials were recorded using sharp microelectrodes. ISO (10 nM) elevated the plateau potential and shortened action potential duration (APD) in subepicardial and mid-myocardial cells, which effects were associated with multifold enhancement of I Ca and I Ks and moderate stimulation of I Kr. The ISO-induced plateau shift and I Ca increase developed faster than the shortening of APD and stimulation of I Ks and I Kr. Blockade of β1-adrenoceptors (using 300 nM CGP-20712A) converted the ISO-induced shortening of APD to lengthening, decreased its latency, and reduced the plateau shift. In contrast, blockade of β2-adrenoceptors (by 50 nM ICI 118,551) augmented the APD-shortening effect and increased the latency of plateau shift without altering its magnitude. All effects of ISO were prevented by simultaneous blockade of both receptor types. Inhibition of phosphodiesterases decreased the differences observed in the turn on of the ISO-induced plateau shift and APD shortening. ISO-induced activation of I Ca is turned on faster than the stimulation of I Ks and I Kr in canine ventricular cells due to the involvement of different adrenergic pathways and compartmentalization.

Original languageEnglish
Pages (from-to)457-467
Number of pages11
JournalNaunyn-Schmiedeberg's Archives of Pharmacology
Volume387
Issue number5
DOIs
Publication statusPublished - 2014

Fingerprint

Isoproterenol
Muscle Cells
Action Potentials
Canidae
Potassium
Calcium
Adrenergic Agents
Adrenergic Receptors
Phosphoric Diester Hydrolases
Microelectrodes
Patch-Clamp Techniques

Keywords

  • Action potential duration
  • Adrenergic activation
  • Calcium current
  • Dog myocytes
  • Potassium currents
  • Signal transduction

ASJC Scopus subject areas

  • Pharmacology
  • Medicine(all)

Cite this

Asynchronous activation of calcium and potassium currents by isoproterenol in canine ventricular myocytes. / Ruzsnavszky, Ferenc; Hegyi, Bence; Kistamás, Kornél; Váczi, Krisztina; Horváth, Balázs; Szentandrássy, N.; Bányász, Tamás; Nánási, P.; Magyar, J.

In: Naunyn-Schmiedeberg's Archives of Pharmacology, Vol. 387, No. 5, 2014, p. 457-467.

Research output: Contribution to journalArticle

Ruzsnavszky, Ferenc ; Hegyi, Bence ; Kistamás, Kornél ; Váczi, Krisztina ; Horváth, Balázs ; Szentandrássy, N. ; Bányász, Tamás ; Nánási, P. ; Magyar, J. / Asynchronous activation of calcium and potassium currents by isoproterenol in canine ventricular myocytes. In: Naunyn-Schmiedeberg's Archives of Pharmacology. 2014 ; Vol. 387, No. 5. pp. 457-467.
@article{739e4da1ab7e4cbb8419478e7bd5f9ab,
title = "Asynchronous activation of calcium and potassium currents by isoproterenol in canine ventricular myocytes",
abstract = "Adrenergic activation of L-type Ca2+ and various K+ currents is a crucial mechanism of cardiac adaptation; however, it may carry a substantial proarrhythmic risk as well. The aim of the present work was to study the timing of activation of Ca2+ and K+ currents in isolated canine ventricular cells in response to exposure to isoproterenol (ISO). Whole cell configuration of the patch-clamp technique in either conventional voltage clamp or action potential voltage clamp modes were used to monitor I Ca, I Ks, and I Kr, while action potentials were recorded using sharp microelectrodes. ISO (10 nM) elevated the plateau potential and shortened action potential duration (APD) in subepicardial and mid-myocardial cells, which effects were associated with multifold enhancement of I Ca and I Ks and moderate stimulation of I Kr. The ISO-induced plateau shift and I Ca increase developed faster than the shortening of APD and stimulation of I Ks and I Kr. Blockade of β1-adrenoceptors (using 300 nM CGP-20712A) converted the ISO-induced shortening of APD to lengthening, decreased its latency, and reduced the plateau shift. In contrast, blockade of β2-adrenoceptors (by 50 nM ICI 118,551) augmented the APD-shortening effect and increased the latency of plateau shift without altering its magnitude. All effects of ISO were prevented by simultaneous blockade of both receptor types. Inhibition of phosphodiesterases decreased the differences observed in the turn on of the ISO-induced plateau shift and APD shortening. ISO-induced activation of I Ca is turned on faster than the stimulation of I Ks and I Kr in canine ventricular cells due to the involvement of different adrenergic pathways and compartmentalization.",
keywords = "Action potential duration, Adrenergic activation, Calcium current, Dog myocytes, Potassium currents, Signal transduction",
author = "Ferenc Ruzsnavszky and Bence Hegyi and Korn{\'e}l Kistam{\'a}s and Krisztina V{\'a}czi and Bal{\'a}zs Horv{\'a}th and N. Szentandr{\'a}ssy and Tam{\'a}s B{\'a}ny{\'a}sz and P. N{\'a}n{\'a}si and J. Magyar",
year = "2014",
doi = "10.1007/s00210-014-0964-6",
language = "English",
volume = "387",
pages = "457--467",
journal = "Naunyn-Schmiedeberg's Archives of Pharmacology",
issn = "0028-1298",
publisher = "Springer Verlag",
number = "5",

}

TY - JOUR

T1 - Asynchronous activation of calcium and potassium currents by isoproterenol in canine ventricular myocytes

AU - Ruzsnavszky, Ferenc

AU - Hegyi, Bence

AU - Kistamás, Kornél

AU - Váczi, Krisztina

AU - Horváth, Balázs

AU - Szentandrássy, N.

AU - Bányász, Tamás

AU - Nánási, P.

AU - Magyar, J.

PY - 2014

Y1 - 2014

N2 - Adrenergic activation of L-type Ca2+ and various K+ currents is a crucial mechanism of cardiac adaptation; however, it may carry a substantial proarrhythmic risk as well. The aim of the present work was to study the timing of activation of Ca2+ and K+ currents in isolated canine ventricular cells in response to exposure to isoproterenol (ISO). Whole cell configuration of the patch-clamp technique in either conventional voltage clamp or action potential voltage clamp modes were used to monitor I Ca, I Ks, and I Kr, while action potentials were recorded using sharp microelectrodes. ISO (10 nM) elevated the plateau potential and shortened action potential duration (APD) in subepicardial and mid-myocardial cells, which effects were associated with multifold enhancement of I Ca and I Ks and moderate stimulation of I Kr. The ISO-induced plateau shift and I Ca increase developed faster than the shortening of APD and stimulation of I Ks and I Kr. Blockade of β1-adrenoceptors (using 300 nM CGP-20712A) converted the ISO-induced shortening of APD to lengthening, decreased its latency, and reduced the plateau shift. In contrast, blockade of β2-adrenoceptors (by 50 nM ICI 118,551) augmented the APD-shortening effect and increased the latency of plateau shift without altering its magnitude. All effects of ISO were prevented by simultaneous blockade of both receptor types. Inhibition of phosphodiesterases decreased the differences observed in the turn on of the ISO-induced plateau shift and APD shortening. ISO-induced activation of I Ca is turned on faster than the stimulation of I Ks and I Kr in canine ventricular cells due to the involvement of different adrenergic pathways and compartmentalization.

AB - Adrenergic activation of L-type Ca2+ and various K+ currents is a crucial mechanism of cardiac adaptation; however, it may carry a substantial proarrhythmic risk as well. The aim of the present work was to study the timing of activation of Ca2+ and K+ currents in isolated canine ventricular cells in response to exposure to isoproterenol (ISO). Whole cell configuration of the patch-clamp technique in either conventional voltage clamp or action potential voltage clamp modes were used to monitor I Ca, I Ks, and I Kr, while action potentials were recorded using sharp microelectrodes. ISO (10 nM) elevated the plateau potential and shortened action potential duration (APD) in subepicardial and mid-myocardial cells, which effects were associated with multifold enhancement of I Ca and I Ks and moderate stimulation of I Kr. The ISO-induced plateau shift and I Ca increase developed faster than the shortening of APD and stimulation of I Ks and I Kr. Blockade of β1-adrenoceptors (using 300 nM CGP-20712A) converted the ISO-induced shortening of APD to lengthening, decreased its latency, and reduced the plateau shift. In contrast, blockade of β2-adrenoceptors (by 50 nM ICI 118,551) augmented the APD-shortening effect and increased the latency of plateau shift without altering its magnitude. All effects of ISO were prevented by simultaneous blockade of both receptor types. Inhibition of phosphodiesterases decreased the differences observed in the turn on of the ISO-induced plateau shift and APD shortening. ISO-induced activation of I Ca is turned on faster than the stimulation of I Ks and I Kr in canine ventricular cells due to the involvement of different adrenergic pathways and compartmentalization.

KW - Action potential duration

KW - Adrenergic activation

KW - Calcium current

KW - Dog myocytes

KW - Potassium currents

KW - Signal transduction

UR - http://www.scopus.com/inward/record.url?scp=84899931689&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84899931689&partnerID=8YFLogxK

U2 - 10.1007/s00210-014-0964-6

DO - 10.1007/s00210-014-0964-6

M3 - Article

C2 - 24566722

AN - SCOPUS:84899931689

VL - 387

SP - 457

EP - 467

JO - Naunyn-Schmiedeberg's Archives of Pharmacology

JF - Naunyn-Schmiedeberg's Archives of Pharmacology

SN - 0028-1298

IS - 5

ER -