SEA0400 fails to alter the magnitude of intracellular Ca2+ transients and contractions in Langendorff-perfused guinea pig heart

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Abstract

SEA0400 is a recently developed inhibitor of the Na+/Ca 2+ exchanger (NCX) shown to suppress both forward and reverse mode operation of NCX. Present experiments were designed to study the effect of partial blockade of NCX on Ca handling and contractility in Langendorff-perfused guinea pig hearts loaded with the fluorescent Ca-sensitive dye fura-2. Left ventricular pressure and intracellular calcium concentration ([Ca 2+]i) were synchronously recorded before and after cumulative superfusion with 0.3 and 1 μM SEA0400. SEA0400 caused no significant change in the systolic and diastolic values of left ventricular pressure and [Ca2+]i. Accordingly, pulse pressure and amplitude of the [Ca2+]i transient also remained unchanged in the presence of SEA0400. SEA0400 had no influence either on the time required to reach peak values of pressure and [Ca2+]i or on half relaxation time. On the other hand, both 0.3 and 1 μM SEA0400 significantly increased the decay time constant of [Ca2+]i transients, obtained by fitting its descending limb between 30% and 90% of relaxation, from 127 ± 7 to 165 ± 7 and 177 ± 14 ms, respectively (P <0.05, n = 6). In contrast to the guinea pig hearts, rat hearts responded to SEA0400 treatment with increased [Ca2+] i transients and contractility. These interspecies differences observed in the effect of SEA0400 can be explained by the known differences in calcium handling between the two species.

Original languageEnglish
Pages (from-to)65-71
Number of pages7
JournalNaunyn-Schmiedeberg's Archives of Pharmacology
Volume378
Issue number1
DOIs
Publication statusPublished - Jul 2008

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Guinea Pigs
Sodium-Calcium Exchanger
Ventricular Pressure
Calcium
SEA 0400
Fura-2
Extremities
Blood Pressure
Pressure

Keywords

  • Contraction
  • Guinea pig heart
  • Intracellular calcium
  • Na/Ca exchange
  • NCX inhibitors
  • SEA0400

ASJC Scopus subject areas

  • Pharmacology

Cite this

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title = "SEA0400 fails to alter the magnitude of intracellular Ca2+ transients and contractions in Langendorff-perfused guinea pig heart",
abstract = "SEA0400 is a recently developed inhibitor of the Na+/Ca 2+ exchanger (NCX) shown to suppress both forward and reverse mode operation of NCX. Present experiments were designed to study the effect of partial blockade of NCX on Ca handling and contractility in Langendorff-perfused guinea pig hearts loaded with the fluorescent Ca-sensitive dye fura-2. Left ventricular pressure and intracellular calcium concentration ([Ca 2+]i) were synchronously recorded before and after cumulative superfusion with 0.3 and 1 μM SEA0400. SEA0400 caused no significant change in the systolic and diastolic values of left ventricular pressure and [Ca2+]i. Accordingly, pulse pressure and amplitude of the [Ca2+]i transient also remained unchanged in the presence of SEA0400. SEA0400 had no influence either on the time required to reach peak values of pressure and [Ca2+]i or on half relaxation time. On the other hand, both 0.3 and 1 μM SEA0400 significantly increased the decay time constant of [Ca2+]i transients, obtained by fitting its descending limb between 30{\%} and 90{\%} of relaxation, from 127 ± 7 to 165 ± 7 and 177 ± 14 ms, respectively (P <0.05, n = 6). In contrast to the guinea pig hearts, rat hearts responded to SEA0400 treatment with increased [Ca2+] i transients and contractility. These interspecies differences observed in the effect of SEA0400 can be explained by the known differences in calcium handling between the two species.",
keywords = "Contraction, Guinea pig heart, Intracellular calcium, Na/Ca exchange, NCX inhibitors, SEA0400",
author = "N. Szentandr{\'a}ssy and P{\'e}ter Birinyi and G. Szigeti and Attila Farkas and J. Magyar and A. T{\'o}th and L. Csernoch and A. Varr{\'o} and P. N{\'a}n{\'a}si",
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T1 - SEA0400 fails to alter the magnitude of intracellular Ca2+ transients and contractions in Langendorff-perfused guinea pig heart

AU - Szentandrássy, N.

AU - Birinyi, Péter

AU - Szigeti, G.

AU - Farkas, Attila

AU - Magyar, J.

AU - Tóth, A.

AU - Csernoch, L.

AU - Varró, A.

AU - Nánási, P.

PY - 2008/7

Y1 - 2008/7

N2 - SEA0400 is a recently developed inhibitor of the Na+/Ca 2+ exchanger (NCX) shown to suppress both forward and reverse mode operation of NCX. Present experiments were designed to study the effect of partial blockade of NCX on Ca handling and contractility in Langendorff-perfused guinea pig hearts loaded with the fluorescent Ca-sensitive dye fura-2. Left ventricular pressure and intracellular calcium concentration ([Ca 2+]i) were synchronously recorded before and after cumulative superfusion with 0.3 and 1 μM SEA0400. SEA0400 caused no significant change in the systolic and diastolic values of left ventricular pressure and [Ca2+]i. Accordingly, pulse pressure and amplitude of the [Ca2+]i transient also remained unchanged in the presence of SEA0400. SEA0400 had no influence either on the time required to reach peak values of pressure and [Ca2+]i or on half relaxation time. On the other hand, both 0.3 and 1 μM SEA0400 significantly increased the decay time constant of [Ca2+]i transients, obtained by fitting its descending limb between 30% and 90% of relaxation, from 127 ± 7 to 165 ± 7 and 177 ± 14 ms, respectively (P <0.05, n = 6). In contrast to the guinea pig hearts, rat hearts responded to SEA0400 treatment with increased [Ca2+] i transients and contractility. These interspecies differences observed in the effect of SEA0400 can be explained by the known differences in calcium handling between the two species.

AB - SEA0400 is a recently developed inhibitor of the Na+/Ca 2+ exchanger (NCX) shown to suppress both forward and reverse mode operation of NCX. Present experiments were designed to study the effect of partial blockade of NCX on Ca handling and contractility in Langendorff-perfused guinea pig hearts loaded with the fluorescent Ca-sensitive dye fura-2. Left ventricular pressure and intracellular calcium concentration ([Ca 2+]i) were synchronously recorded before and after cumulative superfusion with 0.3 and 1 μM SEA0400. SEA0400 caused no significant change in the systolic and diastolic values of left ventricular pressure and [Ca2+]i. Accordingly, pulse pressure and amplitude of the [Ca2+]i transient also remained unchanged in the presence of SEA0400. SEA0400 had no influence either on the time required to reach peak values of pressure and [Ca2+]i or on half relaxation time. On the other hand, both 0.3 and 1 μM SEA0400 significantly increased the decay time constant of [Ca2+]i transients, obtained by fitting its descending limb between 30% and 90% of relaxation, from 127 ± 7 to 165 ± 7 and 177 ± 14 ms, respectively (P <0.05, n = 6). In contrast to the guinea pig hearts, rat hearts responded to SEA0400 treatment with increased [Ca2+] i transients and contractility. These interspecies differences observed in the effect of SEA0400 can be explained by the known differences in calcium handling between the two species.

KW - Contraction

KW - Guinea pig heart

KW - Intracellular calcium

KW - Na/Ca exchange

KW - NCX inhibitors

KW - SEA0400

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JO - Naunyn-Schmiedeberg's Archives of Pharmacology

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