Gangliosides Stimulate Calcium Flux in Neuro‐2A Cells and Require Exogenous Calcium for Neuritogenesis

The neuritogenic effect of exogenous ganglioside has been documented with a variety of neuronal and neuroblastoma systems, but the mechanism is not understood. Involvement of Ca²⁺ is suggested by this study which demonstrates that treatment of Neuro‐2A cells with bovine brain gangliosides (BBG) in Ca²⁺‐depleted medium failed to produce neurite outgrowth. This was in contrast to treatment with retinoic acid or dibutyryl cyclic AMP which induced differentiation under the same conditions. Addition of BBG to Neuro‐2A cells caused small, but significant, increases in both influx and efflux of Ca²⁺. It thus appears that although neuritogenesis can proceed by more than one mechanism, that induced by BBG requires exogenous Ca²⁺ and involves stimulation of Ca²⁺ flux.