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Mechanistic and functional changes in Ca2+ entry after retinoic acid-induced differentiation of neuroblastoma cells

Lookup NU author(s): Dr Anna Brown, Fiona Riddoch, Dr Andrew Robson, Dr Chris RedfernORCiD, Dr Tim Cheek


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We have investigated effects of neuronal differentiation on hormone-induced Ca2+ entry. Fura-2 fluorescence measurements of undifferentiated SH-SY5Y neuroblastoma cells, stimulated with methacholine, revealed the presence of voltage-operated Ca2+-permeable, Mn2+-impermeable entry pathways, and at least two voltage-independent Ca2+- and Mn2+-permeable entry pathways, all of which apparently contribute to both peak and plateau phases of the Ca2+ signal. Similar experiments using 9-cis retinoic acid-differentiated cells, however, revealed voltage-operated Ca2+-permeable, Mn2+-impermeable channels, and, more significantly, the absence or down-regulation of the most predominant of the voltage-independent entry pathways. This down-regulated pathway is probably due to CCE (capacitative Ca2+ entry), since thapsigargin also stimulated Ca2+ and Mn2+ entry in undifferentiated but not differentiated cells. The Ca2+ entry components remaining in methacholine-stimulated differentiated cells contributed to only the plateau phase of the Ca2+ signal. We conclude that differentiation of SH-SY5Y cells results in a mechanistic and functional change in hormone-stimulated Ca2+ entry. In undifferentiated cells, voltage-operated Ca2+ channels, CCE and NCCE (non-CCE) pathways are present. Of the voltage-independent pathways, the predominant one appears to be CCE. These pathways contribute to both peak and plateau phases of the Ca 2+ signal. In differentiated cells, CCE is either absent or down-regulated, whereas voltage-operated entry and NCCE remain active and contribute to only the plateau phase of the Ca2+ signal. © 2005 Biochemical Society.

Publication metadata

Author(s): Brown, A.M., Riddoch, F.C, Robson, A., Redfern, C.P.F., Cheek, T.R.

Publication type: Article

Publication status: Published

Journal: Biochemical Journal

Year: 2005

Volume: 388

Issue: 3

Pages: 941-948

Print publication date: 15/06/2005

ISSN (print): 0264-6021

ISSN (electronic): 1470-8728


DOI: 10.1042/BJ20042127

PubMed id: 15673285


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Funder referenceFunder name
G0000190Medical Research Council