BIPHASIC EFFECT OF CALCIUM ON NEURITE OUTGROWTH IN NEUROBLASTOMA AND CEREBELLAR GRANULE CELLS

We have examined the effect of cytosolic calcium concentration ([Ca2+] (i)) on neurite outgrowth in two neuronal cells, cerebellar granule ce lls and N1E-115 neuroblastoma cells, The set point [Ca2+](i) in unstim ulated cells bathed in normal extracellular medium was 37 nM and 108 n M, respectively. When we altered extracellular calcium concentration t o cause small excursions of [Ca2+](i) either above or below the set po int, neurite outgrowth from granule cells declined. Thus granule cells show the bell-shaped dependence of neurite outgrowth on [Ca2+](i) cha racteristic of sensory and other neurones [Dev. Brain Res., 70 (1992) 287-290; The Axon, Oxford University Press, New York, 1994]. In contra st, neurite outgrowth from N1E-115 cells increased monotonically as [C a2+](i) was reduced. This result, which is consistent with results obt ained by studying individual growth cones [J. Neurosci., 9 (1989) 4007 -4020], implies that these transformed cells are aberrant in having no bell-shaped dependence of neurite outgrowth on [Ca2+](i). In both cel l types an increase of [Ca2+](i) above the set point reduced neurite o utgrowth. However, this decline did not persist as [Ca2+](i) was set t o increasingly high levels by increasing extracellular calcium. Rather , in both cell types, an increase of extracellular calcium above 6.9 m M produced a second, increasing phase of neurite outgrowth.