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

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 micromol/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.