Effect of partial blockade of the Na+/Ca2+-exchanger on Ca2+ handling in isolated rat ventricular myocytes

K. Acsai, Attila Kun, Attila S. Farkas, F. Fülöp, N. Nagy, Marianna Balázs, N. Szentandrássy, P. Nánási, J. Papp, A. Varró, A. Tóth

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Abstract

SEA0400 is a selective inhibitor of the Na+/Ca2+ exchanger having equal potencies to suppress both the forward and reverse mode operation of the Na+/Ca2+ exchanger. Present experiments were designed to study the effect of partial blockade of Na+/Ca2+ exchanger on Ca2+ handling in isolated rat ventricular myocytes. Intracellular Ca2+ transient and cell shortening were measured in ventricular myocytes loaded with Fura-2-AM fluorescent dye. Partial blockade of Na+/Ca2+ exchanger was induced by superfusion of the cells with SEA0400 at a concentration of 0.3 μM. Amplitude of the intracellular Ca2+ transient and cell shortening was significantly increased by SEA0400 in both field stimulated and voltage clamped myocytes, without significant elevation of diastolic Ca2+ level and the decay time constant of the Ca2+ transient. In patch clamped myocytes the SEA0400 induced increase in the Ca2+ transient and cell shortening was accompanied by significant reduction of peak L-type Ca2+ current. These effects can be explained by the autoregulative nature of cardiac Ca2+ handling, as the reduced Ca2+ efflux from the cell results in an increased Ca2+ load to the sarcoplasmic reticulum leading to increased Ca2+ release, which in turn may decrease the L-type Ca2+ current by accelaration of Ca2+ dependent inactivation of L-type Ca2+ current. Our results suggest that complex changes in the Ca2+ cycling can occur after selective pharmacological inhibition of the Na+/Ca2+ exchanger.

Original languageEnglish
Pages (from-to)1-6
Number of pages6
JournalEuropean Journal of Pharmacology
Volume576
Issue number1-3
DOIs
Publication statusPublished - Dec 8 2007

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Muscle Cells
Fura-2
Sarcoplasmic Reticulum
Fluorescent Dyes
Pharmacology
SEA 0400

Keywords

  • Ca handling
  • Cardiac myocytes
  • Na/Ca2 exchanger
  • SEA0400

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience
  • Pharmacology

Cite this

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title = "Effect of partial blockade of the Na+/Ca2+-exchanger on Ca2+ handling in isolated rat ventricular myocytes",
abstract = "SEA0400 is a selective inhibitor of the Na+/Ca2+ exchanger having equal potencies to suppress both the forward and reverse mode operation of the Na+/Ca2+ exchanger. Present experiments were designed to study the effect of partial blockade of Na+/Ca2+ exchanger on Ca2+ handling in isolated rat ventricular myocytes. Intracellular Ca2+ transient and cell shortening were measured in ventricular myocytes loaded with Fura-2-AM fluorescent dye. Partial blockade of Na+/Ca2+ exchanger was induced by superfusion of the cells with SEA0400 at a concentration of 0.3 μM. Amplitude of the intracellular Ca2+ transient and cell shortening was significantly increased by SEA0400 in both field stimulated and voltage clamped myocytes, without significant elevation of diastolic Ca2+ level and the decay time constant of the Ca2+ transient. In patch clamped myocytes the SEA0400 induced increase in the Ca2+ transient and cell shortening was accompanied by significant reduction of peak L-type Ca2+ current. These effects can be explained by the autoregulative nature of cardiac Ca2+ handling, as the reduced Ca2+ efflux from the cell results in an increased Ca2+ load to the sarcoplasmic reticulum leading to increased Ca2+ release, which in turn may decrease the L-type Ca2+ current by accelaration of Ca2+ dependent inactivation of L-type Ca2+ current. Our results suggest that complex changes in the Ca2+ cycling can occur after selective pharmacological inhibition of the Na+/Ca2+ exchanger.",
keywords = "Ca handling, Cardiac myocytes, Na/Ca2 exchanger, SEA0400",
author = "K. Acsai and Attila Kun and Farkas, {Attila S.} and F. F{\"u}l{\"o}p and N. Nagy and Marianna Bal{\'a}zs and N. Szentandr{\'a}ssy and P. N{\'a}n{\'a}si and J. Papp and A. Varr{\'o} and A. T{\'o}th",
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T1 - Effect of partial blockade of the Na+/Ca2+-exchanger on Ca2+ handling in isolated rat ventricular myocytes

AU - Acsai, K.

AU - Kun, Attila

AU - Farkas, Attila S.

AU - Fülöp, F.

AU - Nagy, N.

AU - Balázs, Marianna

AU - Szentandrássy, N.

AU - Nánási, P.

AU - Papp, J.

AU - Varró, A.

AU - Tóth, A.

PY - 2007/12/8

Y1 - 2007/12/8

N2 - SEA0400 is a selective inhibitor of the Na+/Ca2+ exchanger having equal potencies to suppress both the forward and reverse mode operation of the Na+/Ca2+ exchanger. Present experiments were designed to study the effect of partial blockade of Na+/Ca2+ exchanger on Ca2+ handling in isolated rat ventricular myocytes. Intracellular Ca2+ transient and cell shortening were measured in ventricular myocytes loaded with Fura-2-AM fluorescent dye. Partial blockade of Na+/Ca2+ exchanger was induced by superfusion of the cells with SEA0400 at a concentration of 0.3 μM. Amplitude of the intracellular Ca2+ transient and cell shortening was significantly increased by SEA0400 in both field stimulated and voltage clamped myocytes, without significant elevation of diastolic Ca2+ level and the decay time constant of the Ca2+ transient. In patch clamped myocytes the SEA0400 induced increase in the Ca2+ transient and cell shortening was accompanied by significant reduction of peak L-type Ca2+ current. These effects can be explained by the autoregulative nature of cardiac Ca2+ handling, as the reduced Ca2+ efflux from the cell results in an increased Ca2+ load to the sarcoplasmic reticulum leading to increased Ca2+ release, which in turn may decrease the L-type Ca2+ current by accelaration of Ca2+ dependent inactivation of L-type Ca2+ current. Our results suggest that complex changes in the Ca2+ cycling can occur after selective pharmacological inhibition of the Na+/Ca2+ exchanger.

AB - SEA0400 is a selective inhibitor of the Na+/Ca2+ exchanger having equal potencies to suppress both the forward and reverse mode operation of the Na+/Ca2+ exchanger. Present experiments were designed to study the effect of partial blockade of Na+/Ca2+ exchanger on Ca2+ handling in isolated rat ventricular myocytes. Intracellular Ca2+ transient and cell shortening were measured in ventricular myocytes loaded with Fura-2-AM fluorescent dye. Partial blockade of Na+/Ca2+ exchanger was induced by superfusion of the cells with SEA0400 at a concentration of 0.3 μM. Amplitude of the intracellular Ca2+ transient and cell shortening was significantly increased by SEA0400 in both field stimulated and voltage clamped myocytes, without significant elevation of diastolic Ca2+ level and the decay time constant of the Ca2+ transient. In patch clamped myocytes the SEA0400 induced increase in the Ca2+ transient and cell shortening was accompanied by significant reduction of peak L-type Ca2+ current. These effects can be explained by the autoregulative nature of cardiac Ca2+ handling, as the reduced Ca2+ efflux from the cell results in an increased Ca2+ load to the sarcoplasmic reticulum leading to increased Ca2+ release, which in turn may decrease the L-type Ca2+ current by accelaration of Ca2+ dependent inactivation of L-type Ca2+ current. Our results suggest that complex changes in the Ca2+ cycling can occur after selective pharmacological inhibition of the Na+/Ca2+ exchanger.

KW - Ca handling

KW - Cardiac myocytes

KW - Na/Ca2 exchanger

KW - SEA0400

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JO - European Journal of Pharmacology

JF - European Journal of Pharmacology

SN - 0014-2999

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