Trophic effect of cholera toxin B subunit in cultured cerebellar granule neurons: Modulation of intracellular calcium by GM1 ganglioside

G. Wu, Z. H. Lu, K. Nakamura, D. C. Spray, R. W. Ledeen

Research output: Contribution to journalArticlepeer-review

27 Scopus citations

Abstract

Survival of cerebellar granule cells (CGC) in culture was significantly improved in the presence of cholera toxin B subunit (Ctx B), a ligand which binds to GM1 with specificity and high affinity. This trophic effect was linked to elevation of intracellular calcium ([Ca 2+](i)), and was additive to that of high K +. Survival was optimized when Ctx B was present for several days during the early culture period. 45Ca 2+ and cell survival studies indicated the mechanism to involve enhanced influx of Ca 2+ through L-type voltage-sensitive channels, since the trophic effect was blocked by antagonists specific for that channel type. Inhibitors of N-methyl-D- aspartate receptor/channels were without effect. During the early stage of culture Ctx B, together with 25 mM K +, caused [Ca 2+](i) to rise to 0.2- 0.7 μM in a higher proportion of cells than 25 mM K + alone. A significant change in the nature of GM1 modulation of Ca 2+ flux occurred after 7 days in culture, at which time Ctx B ceased to elevate and instead reduced [Ca 2+](i) below the level attained with 25 mM K +. GM1 thus appears to serve as intrinsic inhibitor of one or more L-type Ca 2+ channels during the first 7 days in vitro, and then as intrinsic activator of (possibly other) L- type channels after that period. This is the first demonstration of a modulatory role for GM1 ganglioside affecting Ca 2+ homeostasis in cultured neurons of the CNS.

Original languageEnglish (US)
Pages (from-to)243-254
Number of pages12
JournalJournal of Neuroscience Research
Volume44
Issue number3
DOIs
StatePublished - 1996

Keywords

  • L-type calcium channel
  • calcium modulation
  • cerebellar granule neurons

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience

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