Leukemia inhibitory factor, a potent cardiac hypertrophic cytokine, enhances L-type Ca2+ current and [Ca2+](i) transient in cardiomyocytes

Mitsushige Murata, Keiichi Fukuda, Hideyuki Ishida, Shunichiro Miyoshi, Takahiro Koura, Hiroaki Kodama, Hiroe K. Nakazawa, Satoshi Ogawa

Research output: Contribution to journalArticle

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Abstract

This study investigates whether leukemia inhibitory factor (LIF), a potent cardiac hypertrophic cytokine, affects the L-type Ca2+ current (I(Ca.L)) and intracellular Ca2+ concentrations ([Ca2+](i)) in cardiomyocytes. I(Ca.L) was recorded using a whole cell patch clamp configuration in guinea pig cardiomyocytes, and the [Ca2+](i) transient was detected by use of Fluo-3 in rat cardiomyocytes. Cells were preincubated with LIF (1000 U/ml) for 15 min before whole cell recording. LIF increased I(Ca.L) by 41.8%. LIF synergistically increased I(Ca.L) with isoproterenol. Preincubation with H89 did not inhibit the LIF-induced increase in I(Ca.L), indicating that this phenomenon is PKA-independent. PD98059 completely inhibited the increase in I(Ca.L), and this effect was dose-dependent (IC50 = 3.6 μmol/l). Other signal transduction inhibitors including AG490, SB203580, chelerythrine, genistein, and KN62 did not affect the LIF-induced increase in I(Ca.L). Perforated patch clamp recording revealed that LIF maximally increased the I(Ca.L) by 25% at 15 min. LIF also increased the peak [Ca2+](i) transient level by 63% at 15 min. PD98059 fully inhibited the increase in the [Ca2+](i) transient. In conclusion, LIF increased I(Ca.L) and the [Ca2+](i) transient in cardiomyocytes, and the Raf-1/MEK/ERK pathway might be involved in the modulation of this activation.

Original languageEnglish
Pages (from-to)237-245
Number of pages9
JournalJournal of Molecular and Cellular Cardiology
Volume31
Issue number1
DOIs
Publication statusPublished - 1999 Jan

Fingerprint

Leukemia Inhibitory Factor
Cardiac Myocytes
Cytokines
MAP Kinase Signaling System
Genistein
Patch-Clamp Techniques
Isoproterenol
Inhibitory Concentration 50
Signal Transduction
Guinea Pigs

Keywords

  • [Ca](i) transient
  • Cardiac hypertrophy
  • L-type Ca current
  • Leukemia inhibitory factor
  • Mitogen activated protein kinase

ASJC Scopus subject areas

  • Molecular Biology
  • Cardiology and Cardiovascular Medicine

Cite this

Leukemia inhibitory factor, a potent cardiac hypertrophic cytokine, enhances L-type Ca2+ current and [Ca2+](i) transient in cardiomyocytes. / Murata, Mitsushige; Fukuda, Keiichi; Ishida, Hideyuki; Miyoshi, Shunichiro; Koura, Takahiro; Kodama, Hiroaki; Nakazawa, Hiroe K.; Ogawa, Satoshi.

In: Journal of Molecular and Cellular Cardiology, Vol. 31, No. 1, 01.1999, p. 237-245.

Research output: Contribution to journalArticle

Murata, Mitsushige ; Fukuda, Keiichi ; Ishida, Hideyuki ; Miyoshi, Shunichiro ; Koura, Takahiro ; Kodama, Hiroaki ; Nakazawa, Hiroe K. ; Ogawa, Satoshi. / Leukemia inhibitory factor, a potent cardiac hypertrophic cytokine, enhances L-type Ca2+ current and [Ca2+](i) transient in cardiomyocytes. In: Journal of Molecular and Cellular Cardiology. 1999 ; Vol. 31, No. 1. pp. 237-245.
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abstract = "This study investigates whether leukemia inhibitory factor (LIF), a potent cardiac hypertrophic cytokine, affects the L-type Ca2+ current (I(Ca.L)) and intracellular Ca2+ concentrations ([Ca2+](i)) in cardiomyocytes. I(Ca.L) was recorded using a whole cell patch clamp configuration in guinea pig cardiomyocytes, and the [Ca2+](i) transient was detected by use of Fluo-3 in rat cardiomyocytes. Cells were preincubated with LIF (1000 U/ml) for 15 min before whole cell recording. LIF increased I(Ca.L) by 41.8{\%}. LIF synergistically increased I(Ca.L) with isoproterenol. Preincubation with H89 did not inhibit the LIF-induced increase in I(Ca.L), indicating that this phenomenon is PKA-independent. PD98059 completely inhibited the increase in I(Ca.L), and this effect was dose-dependent (IC50 = 3.6 μmol/l). Other signal transduction inhibitors including AG490, SB203580, chelerythrine, genistein, and KN62 did not affect the LIF-induced increase in I(Ca.L). Perforated patch clamp recording revealed that LIF maximally increased the I(Ca.L) by 25{\%} at 15 min. LIF also increased the peak [Ca2+](i) transient level by 63{\%} at 15 min. PD98059 fully inhibited the increase in the [Ca2+](i) transient. In conclusion, LIF increased I(Ca.L) and the [Ca2+](i) transient in cardiomyocytes, and the Raf-1/MEK/ERK pathway might be involved in the modulation of this activation.",
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AU - Miyoshi, Shunichiro

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AB - This study investigates whether leukemia inhibitory factor (LIF), a potent cardiac hypertrophic cytokine, affects the L-type Ca2+ current (I(Ca.L)) and intracellular Ca2+ concentrations ([Ca2+](i)) in cardiomyocytes. I(Ca.L) was recorded using a whole cell patch clamp configuration in guinea pig cardiomyocytes, and the [Ca2+](i) transient was detected by use of Fluo-3 in rat cardiomyocytes. Cells were preincubated with LIF (1000 U/ml) for 15 min before whole cell recording. LIF increased I(Ca.L) by 41.8%. LIF synergistically increased I(Ca.L) with isoproterenol. Preincubation with H89 did not inhibit the LIF-induced increase in I(Ca.L), indicating that this phenomenon is PKA-independent. PD98059 completely inhibited the increase in I(Ca.L), and this effect was dose-dependent (IC50 = 3.6 μmol/l). Other signal transduction inhibitors including AG490, SB203580, chelerythrine, genistein, and KN62 did not affect the LIF-induced increase in I(Ca.L). Perforated patch clamp recording revealed that LIF maximally increased the I(Ca.L) by 25% at 15 min. LIF also increased the peak [Ca2+](i) transient level by 63% at 15 min. PD98059 fully inhibited the increase in the [Ca2+](i) transient. In conclusion, LIF increased I(Ca.L) and the [Ca2+](i) transient in cardiomyocytes, and the Raf-1/MEK/ERK pathway might be involved in the modulation of this activation.

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