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

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35 Citations (Scopus)


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
Issue number1
Publication statusPublished - 1999 Jan


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

ASJC Scopus subject areas

  • Molecular Biology
  • Cardiology and Cardiovascular Medicine


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