title: GABA(A) receptor in growth cones: the outline of GABA(A) receptor-dependent signaling in growth cones is applicable to a variety of alpha-subunit species.
abstract: The growth cone is responsible for axonal elongation and pathfinding by responding to various modulators for neurite growth, including neurotransmitters. We demonstrated an outline of the gamma aminobutyric acid (GABA)(A)-dependent signaling in growth cones. Here, we examined the effects of the modulators of GABA(A) receptor on the signaling in growth cones. Phenobarbital or propofol, acting on beta-subunit, enhanced the [Cl(-)]infi change and [Ca(2+)](i) elevation by the GABA stimulation to isolated growth cones. Besides, propofol enhanced GABA-dependent phosphorylation of growth-associated protein of 43 kDa (GAP-43) by protein kinase C. In contrast, an alpha-subunit acting agent diazepam did not modulate any of the above signals. Next, we examined the effect of the developmental change of alpha-subunit on the outline of the GABA(A)-dependent signaling in growth cones. We also found that the amounts of several different alpha-subunit isoforms developmentally increased or decreased in growth cone membrane (GCM), but that the affinity and density of the [(3)H]diazepam binding sites were similar to those in adult synaptic membrane. Taken together, our results strongly suggest that each step of GABA(A)-dependent signaling in GCM is not modified by diazepam, indicating that the signaling pathway mediated by GABA(A) receptor in growth cones is applicable to any compositional change of alpha-subunit isoforms.
authors.affiliation: Department of Molecular and Cellular Neurobiology, Gunma University School of Medicine, Maebashi, Gunma, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Fukura
authors.forename: Y
authors.initials: Y
authors.lastname: Kitani
authors.forename: Y
authors.initials: Y
authors.lastname: Komiya
authors.forename: M
authors.initials: M
authors.lastname: Igarashi
mesh_terms: D000375:Aging / Q000502:physiology*; D000818:Animals; D000831:Animals, Newborn; D002118:Calcium / Q000378:metabolism; D002540:Cerebral Cortex / Q000502:physiology; D002712:Chlorides / Q000378:metabolism; D003975:Diazepam / Q000494:pharmacology; D005333:Fetus; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D010634:Phenobarbital / Q000494:pharmacology; D015742:Propofol / Q000494:pharmacology; D016548:Prosencephalon / Q000254:growth & development / Q000502:physiology*; D020033:Protein Isoforms / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D011963:Receptors, GABA-A / Q000187:drug effects / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology*; D013570:Synaptic Membranes / Q000502:physiology; D005680:gamma-Aminobutyric Acid / Q000494:pharmacology
chemical_list: D002712:Chlorides; D020033:Protein Isoforms; D011963:Receptors, GABA-A; D005680:gamma-Aminobutyric Acid; D003975:Diazepam; D002118:Calcium; D015742:Propofol; D010634:Phenobarbital