M. Murata et al., Leukemia inhibitory factor, a potent cardiac hypertrophic cytokine, enhances L-type Ca2+ current and [Ca2+](i) transient in cardiomyocytes, J MOL CEL C, 31(1), 1999, pp. 237-245
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.