Characterization of spontaneous calcium transients in nerve growth cones and their effect on growth cone migration

This study examines the mechanisms of spontaneous and induced [Ca 2+] i spiking in nerve growth cones and the effect of spikes on growth cone migration. Over a 10–20 min observation period, 29% of DRG growth cones undergo spontaneous and transient elevations in physiological extracellular Ca 2+ ((Ca 2+) o; 2 mM), whereas 67% of growth cones exposed to 20 mM (Ca 2+) o exhibit similar [Ca 2+] i spikes. Spontaneous [Ca 2+] 1 spiking was not observed in neuronal cell bodies or nonneuronal cells. Ca 2+ influx through nonvoltage-gated Ca 2+ channels was required for spontaneous [Ca 2+], spikes in growth cones, since removal of (Ca 2+) o, or addition of the general Ca 2+ channel blockers La 3+ or Ni 2+, reversibly blocked [Ca 2+] 1 spiking, while blockers of the voltage-gated Ca 2+ channels did not. Experiments using agents that influence intracellular Ca 2+ stores suggest that Ca 2+ stores may buffer and release Ca 2+ during growth cone [Ca 2+] 1 spikes. Growth cone migration was immediately and transiently inhibited by [Ca 2+] i spikes, but eventually returned to prespike rates.