Electrically and chemically mediated increases in intracellular calcium in neuronal growth cones

Abstract

In the present report we used the calcium indicator fura-2 to compare intracellular levels of free calcium in growth cones of isolated Helisoma neurons under a variety of experimental conditions. We tested whether 2 different signals that inhibit growth cone motility--action potentials and serotonin--changed calcium levels in growth cones. Electrical stimulation of the cell body caused a rise in calcium levels at the growth cone. After brief stimulation, calcium levels quickly recovered to normal values, whereas longer stimulation periods required longer recovery times. The application of serotonin to growth cones caused an increase in calcium levels that was selective for growth cones of neurons whose outgrowth was inhibited by serotonin, but not for neurons whose outgrowth was not affected. We also found that motile growth cones had higher free calcium levels than growth cones that had spontaneously stopped growing. Furthermore, the distribution of calcium in neurons that contained motile growth cones was heterogeneous; calcium levels were always higher in the growth cone than in the neurite or soma. These data indicate that calcium levels in growth cones vary in different states of outgrowth and that calcium levels can be modulated by both electrical and chemical signals.

Outgrowth-regulating actions of glutamate in isolated hippocampal pyramidal neurons

“…Cellular mechanism of glutamate action Several lines of evidence have implicated calcium as a mediator of the effects of neurotransmitters and electrical activity on neuronal outgrowth (Cohan et al, 1987;Mattson andKater, 1987, Mattson et al, 1987) and survival (Coyle et al, 198 1;Berdichevsky et al, 1983;Coyle et al, 1981;Donaldson et al, 1983;Mayer and Westbrook, 1987). Studies in invertebrate central neurons demonstrated that serotonin and electrical activity can suppress neurite outgrowth by causing calcium influx (Cohan et al, 1987;Mattson and Kater, 1987).…”

“…Studies in invertebrate central neurons demonstrated that serotonin and electrical activity can suppress neurite outgrowth by causing calcium influx (Cohan et al, 1987;Mattson and Kater, 1987). Serotonin apparently induced calcium influx by activating voltage-dependent calcium channels.…”

“…Calcium involvement in the efects of glutamate on outgrowth and survival Neurotransmitter-induced influx of calcium from the cell exterior mediates the suppresive effects of serotonin on neurite outgrowth from identified molluscan neurons (Cohan et al, 1987;Mattson and Kater, 1987). One proposed cellular mechanism whereby EAAs exert their toxic effects is by depolarizationinduced calcium influx (Coyle et al, 198 1;Berdichevsky et al, 1983;Mayer and Westbrook, 1987).…”

“…In addition, one model for the cellular basis of EAA toxicity implicates Ca*+ entry through ion channels activated by the EAA (e.g., Berdi-chevsky et al, 1983;Retz and Coyle, 1984). In molluscan neurons, the cellular mechanism of action of the neurotransmitters mediating outgrowth responses has been more directly addressed and clearly involves neurotransmitter-induced calcium influx from the cell exterior (Cohan et al, 1987;Mattson and Kater, 1987;Mattson et al, 1988).…”

Group I Metabotropic Glutamate Receptors mGluR1α and mGluR5a: Localization in Both Synaptic Layers of the Rat Retina

“…In contrast to different brain regions, where a downregulation was observed for mGluR5 (Romano et al, 1996), mGluR1␣ and mGluR5a were upregulated during postnatal retinal development. It has been shown that intracellular levels of free Ca 2ϩ influence neurite elongation and growth cone movement during development (Cohan et al, 1987) and that group I mGluRs are important for neuronal survival during development (Nicoletti et al, 1996;Pizzi et al, 1996). Because of the early appearance of group I mGluRs before synaptogenesis in the rat retina, they could influence synaptic differentiation during postnatal development and also might play …”