Leukemia Inhibitory Factor, a Potent Cardiac Hypertrophic Cytokine, Enhances L-type Ca2+Current and [Ca2+]iTransient in Cardiomyocytes

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