Appearance of depolarization- and maitotoxin-induced [Ca2+]i elevation in single LAN-1 human neuroblastoma cells on exposure to retinoic acid

Alessandro Fatatis, Antonella Bassi, Elodia Iannotti, Nino Caso, Gustavo D. Mita, Gianfranco Di Renzo, Lucio Annunziato

Research output: Contribution to journalArticlepeer-review


LAN-1 is a human neuroblastoma cell line that, in the undifferentiated state, does not respond to membrane depolarization with an elevation of [Ca2+]i, monitored by fura-2 single-cell microfluorimetry. The exposure of LAN-1 cells to the differentiating agent retinoic acid induced the appearance of [Ca2+], elevation elicited by 55 mM K+. Maitotoxin, a putative activator of voltage-sensitive Ca2+ channels, did not evoke an elevation of [Ca2+]i in undifferentiated LAN-1 cells, but produced a marked and sustained increase in [Ca2+]i, when superfused in retinoic acid-treated cells. Both high K+- and maitotoxin-induced [Ca2+]i elevation in retinoic acid-differentiated LAN-1 cells was reversed by the lanthanide Gd3+, an inorganic Ca2+-entry blocker, and by the snail toxin ω-conotoxin GVIA, which interacts with the N subtype of voltage-sensitive Ca2+ channels. In contrast, both Bay K 8644 and nimodipine, dihydropyridines that selectively activate or block, respectively, the L-channel subtype, were completely ineffective. The tumor promoter phorbol 12-myristate 13-acetate (100 nM), a protein kinase C activator, inhibited the elevation of [Ca2+]i due to Ca2+ influx elicited by membrane depolarization. K+-induced [Ca2+]i elevation appeared 24 h after the addition of retinoic acid and reached the highest magnitude after 72 h. Furthermore, 8 days after the removal of the differentiating agent from the culture medium, the high K+-induced increase of [Ca2+]i was still present. In conclusion, the results of the present study demonstrated that retinoic acid-induced differentiation of LAN-1 cells, which lack a high K+-evoked [Ca2+]i increase in the undifferentiated state, induces the functional expression of an ω-conotoxin GVIA-sensitive, dihydropyridine-insensitive N-type voltage-sensitive Ca2+ channel that can be activated by maitotoxin and negatively modulated by protein kinase C.

Original languageEnglish
Pages (from-to)1900-1907
Number of pages8
JournalJournal of Neurochemistry
Issue number5
Publication statusPublished - Nov 1994


  • Human neuroblastoma
  • LAN-1 cells
  • Maitotoxin
  • Retinoic acid
  • Voltage-sensitive Ca channels

ASJC Scopus subject areas

  • Biochemistry
  • Cellular and Molecular Neuroscience


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