title: Calcium regulation of neurite elongation and growth cone motility.
abstract: 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+.
mesh_terms: D000818:Animals; D000001:Calcimycin / Q000494:pharmacology; D002118:Calcium / Q000502:physiology*; D002121:Calcium Channel Blockers / Q000494:pharmacology; D009474:Neurons / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D012908:Snails
chemical_list: D002121:Calcium Channel Blockers; D000001:Calcimycin; D002118:Calcium