Activin A and all-trans-retinoic acid cooperatively enhanced the functional activity of L-type Ca2+ channels in the neuroblastoma C1300 cell line.
Activin, a member of the transforming growth factor-beta superfamily, regulates various physiological functions. In the present study, we investigated the effect of activin on neuronal differentiation, particularly the functional activity of voltage-dependent Ca2+ channels, in murine neuroblastoma C1300 cells. A slight K(+)-induced increase in the intracellular free Ca2+ ([Ca2+]i) was observed in C1300 cells untreated and treated with either activin A or all-trans-retinoic acid, while treatment with both agents significantly enhanced the increase. The [Ca2+]i increases potentiated by activin A and all-trans-retinoic acid were nearly abolished in the presence of 1.0 mM nickel or in the absence of extracellular Ca2+. Nifedipine (0.1 microM) and omega-conotoxin (1.0 microM), inhibitors of L- and N-type Ca2+ channels, respectively, partially inhibited these responses, however the inhibitory effects of these compounds were not additive. In addition, Bay K 8644, an activator of L-type Ca2+ channels, enhanced the K(+)-induced [Ca2+]i increase. These findings indicated that depolarization evoked the Ca2+ influx, at least in part, through L-type Ca2+ channels in C1300 cells treated with both activin A and all-trans-retinoic acid.
Fukuhara
S
S
Institute of Applied Biochemistry, University of Tsukuba, Ibaraki, Japan.
Mukai
H
H
Munekata
E
E
D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester / Q000494:pharmacology; D028341:Activins; D000818:Animals; D002118:Calcium / Q000378:metabolism; D002120:Calcium Channel Agonists / Q000494:pharmacology; D015220:Calcium Channels / Q000187:drug effects*; D020746:Calcium Channels, L-Type; D002454:Cell Differentiation; D004357:Drug Synergism; D006133:Growth Substances / Q000494:pharmacology*; D007265:Inhibins / Q000494:pharmacology*; D007536:Isomerism; D051379:Mice; D009419:Nerve Tissue Proteins / Q000187:drug effects*; D009447:Neuroblastoma; D009474:Neurons / Q000502:physiology; D011188:Potassium / Q000494:pharmacology; D014212:Tretinoin / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
D002120:Calcium Channel Agonists; D015220:Calcium Channels; D020746:Calcium Channels, L-Type; D006133:Growth Substances; D009419:Nerve Tissue Proteins; D028341:Activins; D014212:Tretinoin; D007265:Inhibins; D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester; D011188:Potassium; D002118:Calcium