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,I-L) a nd intracellular Ca2+ concentrations ([Ca2+](i)) in cardiomyocytes. I-Ca,I- L was recorded using a whole cell patch clamp configuration in guinea pig c ardiomyocytes, 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 mi n before whole cell recording. LIF increased I-Ca,I-L by 41.8%. LIF synergi stically increased I-Ca,I-L with isoproterenol, Preincubation with H89 did not inhibit the LIP-induced increase in I-Ca,I-L, indicating that this phen omenon is PI(A-independent. PD98059 completely inhibited the increase in I- Ca,I-L, and this effect was dose-dependent (IC50 = 3.6 mu mol/l). Other sig nal transduction inhibitors including AG490, SB203580, chelerythrine, genis tein, and KN62 did not affect the LIF-induced increase in I-Ca,I-L. Perfora ted patch clamp recording revealed that LIF maximally increased the I-Ca,I- L by 25% at 15 min. LIF also increased the peak [Ca2+](i) transient level b y 63% at 15 min. PD98059 fully inhibited the increase in the [Ca2+](i) tran sient, In conclusion, LIF increased I-Ca,I-L and the [Ca2+](i) transient in cardiomyocytes and the Raf-1/MEK/ERK pathway might be involved in the modu lation of this activation. (C) 1999 Academic Press.