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Journal of Neuroscience, Vol 7, 4034-4043, Copyright © 1987 by Society for Neuroscience
Calcium regulation of neurite elongation and growth cone motility
MP Mattson and SB Kater
Department of Anatomy, Colorado State University, Fort Collins 80523.
Neurite outgrowth from isolated, identified molluscan (Helisoma trivolvis)
neurons in culture can be suppressed by neurotransmitters and electrical
activity, both of which increase intraneuronal Ca2+ levels (Haydon et al.,
1984; Cohan et al., 1986, 1987). We explored the possibility of a causal
relationship between Ca2+ influx from the cell exterior and neurite
outgrowth using a spectrum of pharmacological manipulations known to affect
transmembrane Ca2+ flux. Ca2+ ionophore A23187, an agent expected to
increase Ca2+ influx, suppressed both elongation and motile growth cone
structures (i.e., filopodia and lamellipodia) in a dose-dependent
(10(8)-10(6) M) and reversible manner. Furthermore, high concentrations of
Ca2+ channel blockers (La3+, Cd2+, Co2+; e.g., 10(-4) M La3+) suppressed
both elongation and growth cone movements. These data support previous
experiments, which indicated that neurite outgrowth is dependent upon a
specific range of intracellular Ca2+ concentrations (Connor, 1986; Cohan et
al., 1987). However, tests of the dose-dependency of the effects of Ca2+
channel blockers on outgrowth revealed that specific, low concentrations of
Ca2+ channel blockers (e.g., 10(-5) M La3+) caused, simultaneously, a
reduction of growth cone filopodia and an acceleration of elongation.
Consistent with the results using low levels of Ca2+ channel blockers,
reduced extracellular Ca2+-stimulated neurite elongation while suppressing
growth cone motility. Finally, neurotransmitter regulation of neurite
outgrowth was shown to require influx of extracellular Ca2+; serotonin
inhibition of neuron B19 was prevented by La3+ (10(-5) M) or by incubation
in a reduced Ca2+ environment. Taken together, these results indicate that
there are optimum levels of Ca2+ influx that promote normal neurite
elongation and growth cone movements; these 2 components of outgrowth
appear to have differential sensitivities to Ca2+.
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