Effects of SEA0400 and KB-R7943 on Na+/Ca2+ exchange current and L-type Ca2+ current in canine ventricular cardiomyocytes

Péter Birinyi, K. Acsai, Tamás Bányász, A. Tóth, Balázs Horváth, L. Virág, N. Szentandrássy, J. Magyar, A. Varró, F. Fülöp, P. Nánási

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Abstract

SEA0400 and KB-R7943 are compounds synthesised to block transsarcolemmal Na+/Ca2+ exchange current (INa/Ca); however, they Have also been shown to inhibit L-type Ca2+ current (I Ca). The potential value of these compounds depends critically on their relative selectivity for INa/Ca over ICa. In the present work, therefore, the concentration-dependent effects of SEA0400 and KB-R7943 on INa/Ca and ICa were studied and compared in canine ventricular cardiomyocytes using the whole-cell configuration of the patch clamp technique. SEA0400 and KB-R7943 decreased INa/Ca in a concentration-dependent manner, having EC50 values of 111±43 nM and 3.35±0.82 μM, when suppressing inward currents, while the respective EC50 values were estimated at 108±18 nM and 4.74±0.69 μM in the case of outward current block. SEA0400 and KB-R7943 also blocked ICa, having comparable EC50 values (3.6 μM and 3.2 μM, respectively). At higher concentrations (10 μM) both drugs accelerated inactivation of ICa, retarded recovery from inactivation and shifted the voltage dependence of inactivation towards more negative voltages. The voltage dependence of activation was slightly modified by SEA0400, but not by KB-R7943. Based on the relatively good selectivity of submicromolar concentrations of SEA0400-but not KB-R7943-for INa/Ca over ICa, SEA0400 appears to be a suitable tool to study the role of INa/Ca in Ca2+ handling in canine cardiac cells. At concentrations higher than 1 μM, however, ICa is progressively suppressed by the compound.

Original languageEnglish
Pages (from-to)63-70
Number of pages8
JournalNaunyn-Schmiedeberg's Archives of Pharmacology
Volume372
Issue number1
DOIs
Publication statusPublished - Jul 2005

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Cardiac Myocytes
Canidae
Patch-Clamp Techniques
2-(2-(4-(4-nitrobenzyloxy)phenyl)ethyl)isothiourea methanesulfonate
SEA 0400
Pharmaceutical Preparations

Keywords

  • Ca current
  • Cardiac cells
  • Dog
  • KB-R7943
  • Na/Ca exchanger
  • SEA0400
  • Voltage clamp

ASJC Scopus subject areas

  • Pharmacology

Cite this

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title = "Effects of SEA0400 and KB-R7943 on Na+/Ca2+ exchange current and L-type Ca2+ current in canine ventricular cardiomyocytes",
abstract = "SEA0400 and KB-R7943 are compounds synthesised to block transsarcolemmal Na+/Ca2+ exchange current (INa/Ca); however, they Have also been shown to inhibit L-type Ca2+ current (I Ca). The potential value of these compounds depends critically on their relative selectivity for INa/Ca over ICa. In the present work, therefore, the concentration-dependent effects of SEA0400 and KB-R7943 on INa/Ca and ICa were studied and compared in canine ventricular cardiomyocytes using the whole-cell configuration of the patch clamp technique. SEA0400 and KB-R7943 decreased INa/Ca in a concentration-dependent manner, having EC50 values of 111±43 nM and 3.35±0.82 μM, when suppressing inward currents, while the respective EC50 values were estimated at 108±18 nM and 4.74±0.69 μM in the case of outward current block. SEA0400 and KB-R7943 also blocked ICa, having comparable EC50 values (3.6 μM and 3.2 μM, respectively). At higher concentrations (10 μM) both drugs accelerated inactivation of ICa, retarded recovery from inactivation and shifted the voltage dependence of inactivation towards more negative voltages. The voltage dependence of activation was slightly modified by SEA0400, but not by KB-R7943. Based on the relatively good selectivity of submicromolar concentrations of SEA0400-but not KB-R7943-for INa/Ca over ICa, SEA0400 appears to be a suitable tool to study the role of INa/Ca in Ca2+ handling in canine cardiac cells. At concentrations higher than 1 μM, however, ICa is progressively suppressed by the compound.",
keywords = "Ca current, Cardiac cells, Dog, KB-R7943, Na/Ca exchanger, SEA0400, Voltage clamp",
author = "P{\'e}ter Birinyi and K. Acsai and Tam{\'a}s B{\'a}ny{\'a}sz and A. T{\'o}th and Bal{\'a}zs Horv{\'a}th and L. Vir{\'a}g and N. Szentandr{\'a}ssy and J. Magyar and A. Varr{\'o} and F. F{\"u}l{\"o}p and P. N{\'a}n{\'a}si",
year = "2005",
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T1 - Effects of SEA0400 and KB-R7943 on Na+/Ca2+ exchange current and L-type Ca2+ current in canine ventricular cardiomyocytes

AU - Birinyi, Péter

AU - Acsai, K.

AU - Bányász, Tamás

AU - Tóth, A.

AU - Horváth, Balázs

AU - Virág, L.

AU - Szentandrássy, N.

AU - Magyar, J.

AU - Varró, A.

AU - Fülöp, F.

AU - Nánási, P.

PY - 2005/7

Y1 - 2005/7

N2 - SEA0400 and KB-R7943 are compounds synthesised to block transsarcolemmal Na+/Ca2+ exchange current (INa/Ca); however, they Have also been shown to inhibit L-type Ca2+ current (I Ca). The potential value of these compounds depends critically on their relative selectivity for INa/Ca over ICa. In the present work, therefore, the concentration-dependent effects of SEA0400 and KB-R7943 on INa/Ca and ICa were studied and compared in canine ventricular cardiomyocytes using the whole-cell configuration of the patch clamp technique. SEA0400 and KB-R7943 decreased INa/Ca in a concentration-dependent manner, having EC50 values of 111±43 nM and 3.35±0.82 μM, when suppressing inward currents, while the respective EC50 values were estimated at 108±18 nM and 4.74±0.69 μM in the case of outward current block. SEA0400 and KB-R7943 also blocked ICa, having comparable EC50 values (3.6 μM and 3.2 μM, respectively). At higher concentrations (10 μM) both drugs accelerated inactivation of ICa, retarded recovery from inactivation and shifted the voltage dependence of inactivation towards more negative voltages. The voltage dependence of activation was slightly modified by SEA0400, but not by KB-R7943. Based on the relatively good selectivity of submicromolar concentrations of SEA0400-but not KB-R7943-for INa/Ca over ICa, SEA0400 appears to be a suitable tool to study the role of INa/Ca in Ca2+ handling in canine cardiac cells. At concentrations higher than 1 μM, however, ICa is progressively suppressed by the compound.

AB - SEA0400 and KB-R7943 are compounds synthesised to block transsarcolemmal Na+/Ca2+ exchange current (INa/Ca); however, they Have also been shown to inhibit L-type Ca2+ current (I Ca). The potential value of these compounds depends critically on their relative selectivity for INa/Ca over ICa. In the present work, therefore, the concentration-dependent effects of SEA0400 and KB-R7943 on INa/Ca and ICa were studied and compared in canine ventricular cardiomyocytes using the whole-cell configuration of the patch clamp technique. SEA0400 and KB-R7943 decreased INa/Ca in a concentration-dependent manner, having EC50 values of 111±43 nM and 3.35±0.82 μM, when suppressing inward currents, while the respective EC50 values were estimated at 108±18 nM and 4.74±0.69 μM in the case of outward current block. SEA0400 and KB-R7943 also blocked ICa, having comparable EC50 values (3.6 μM and 3.2 μM, respectively). At higher concentrations (10 μM) both drugs accelerated inactivation of ICa, retarded recovery from inactivation and shifted the voltage dependence of inactivation towards more negative voltages. The voltage dependence of activation was slightly modified by SEA0400, but not by KB-R7943. Based on the relatively good selectivity of submicromolar concentrations of SEA0400-but not KB-R7943-for INa/Ca over ICa, SEA0400 appears to be a suitable tool to study the role of INa/Ca in Ca2+ handling in canine cardiac cells. At concentrations higher than 1 μM, however, ICa is progressively suppressed by the compound.

KW - Ca current

KW - Cardiac cells

KW - Dog

KW - KB-R7943

KW - Na/Ca exchanger

KW - SEA0400

KW - Voltage clamp

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