Journal of Neuroscience, Vol 9, 4007-4020, Copyright © 1989 by Society for Neuroscience
Elevated cytosolic calcium in the growth cone inhibits neurite elongation in neuroblastoma cells: correlation of behavioral states with cytosolic calcium concentration
RA Silver, AG Lamb and SR Bolsover
Department of Physiology, University College London, United Kingdom.
Schubert (1984) and Kater et al. (1988) have suggested that motility and
growth at the neuronal growth cone is activated by an increase of cytosolic
free calcium concentration ([Ca2+]i) above the levels found in quiescent
growth cones. In order to test this model, we have used a digital imaging
fluorescence microscope together with injection of the fluorescent
indicator dye Fura-2 to measure [Ca2+]i in growth cones of a mammalian
sympathetic neuron, the N1E-115 neuroblastoma cell. The behavior of
individual growth cones, together with spontaneously varying levels of
[Ca2+]i within the growth cone, were monitored for periods of up to several
hours. [Ca2+]i in motile, advancing growth cones was low and equal to
[Ca2+]i in quiescent growth cones. Higher values of [Ca2+]i were found in
motile growth cones that were not advancing, suggesting that a small
elevation of [Ca2+]i inhibits neurite extension. A further rise of [Ca2+]i
above the level found in motile, nonadvancing growth cones appeared to
inhibit motility and cause retraction of the growth cone back towards the
cell body. Spatial gradients of [Ca2+]i within the growth cone were small
and, where statistically significant, [Ca2+]i was lower by 5-10 nM in
motile regions. Our results are incompatible with the model that a rise of
[Ca2+]i is responsible for activating quiescent growth cones; however, our
results suggest that in active growth cones [Ca2+]i can regulate morphology
and behavior.
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