title: Glutamate regulates neurite outgrowth of cultured descending brain neurons from larval lamprey.
abstract: In larval lamprey, descending brain neurons, which regenerate their axons following spinal cord injury, were isolated and examined in cell culture to identify some of the factors that regulate neurite outgrowth. Focal application of 5 mM or 25 mM L-glutamate to single growth cones inhibited outgrowth of the treated neurite, but other neurites from the same neuron were not inhibited, an effect that has not been well studied for neurons in other systems. Glutamate-induced inhibition of neurite outgrowth was abolished by 10 mM kynurenic acid. Application of high potassium media to growth cones inhibited neurite outgrowth, an effect that was blocked by 2 mM cobalt or 100 microM cadmium, suggesting that calcium influx via voltage-gated channels contributes to glutamate-induced regulation of neurite outgrowth. Application of glutamate to growth cones in the presence of 2 microM omega-conotoxin MVIIC (CTX) still inhibited neurite outgrowth, while CTX blocked high potassium-induced inhibition of neurite outgrowth. Thus, CTX blocked virtually all of the calcium influx resulting from depolarization. To our knowledge, this is the first direct demonstration that calcium influx via ligand-gated ion channels can contribute to regulation of neurite outgrowth. Finally, focal application of glutamate to the cell bodies of descending brain neurons inhibited outgrowth of multiple neurites from the same neuron, and this is the first demonstration that multiple neurites can be regulated in this fashion. Signaling mechanisms involving intracellular calcium, similar to those shown here, may be important for regulating axonal regeneration following spinal cord injury in the lamprey.
authors: Interdisciplinary Neuroscience Program, University of Missouri, Columbia, Missouri 65211, USA.
authors: Sarah K
authors: SK
authors: Ryan
authors: Lindsay R
authors: LR
authors: Shotts
authors: Soo-Kyung
authors: SK
authors: Hong
authors: Deepika
authors: D
authors: Nehra
authors: Carl R
authors: CR
authors: Groat
authors: Jon R
authors: JR
authors: Armstrong
authors: Andrew D
authors: AD
authors: McClellan
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D001921:Brain / Q000166:cytology*; D002104:Cadmium / Q000494:pharmacology; D002121:Calcium Channel Blockers / Q000494:pharmacology; D002478:Cells, Cultured; D003035:Cobalt / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D018698:Glutamic Acid / Q000494:pharmacology*; D020439:Growth Cones / Q000187:drug effects; D007736:Kynurenic Acid / Q000494:pharmacology; D007798:Lampreys / Q000033:anatomy & histology; D007814:Larva; D016501:Neurites / Q000187:drug effects*; D009475:Neurons, Afferent / Q000166:cytology*; D011188:Potassium / Q000494:pharmacology; D013997:Time Factors; D020960:omega-Conotoxins / Q000494:pharmacology
chemical_list: D002121:Calcium Channel Blockers; D018691:Excitatory Amino Acid Antagonists; D020960:omega-Conotoxins; D002104:Cadmium; C075851:omega-conotoxin-MVIIC; D003035:Cobalt; D018698:Glutamic Acid; D007736:Kynurenic Acid; D011188:Potassium