title: GABA, GABA receptors and benzodiazepine receptors in the human spinal cord: an autoradiographic and immunohistochemical study at the light and electron microscopic levels.
abstract: The regional, cellular and subcellular distribution of GABA, GABA receptors and benzodiazepine receptors was investigated by light and electron microscopy in the human lumbar spinal cord taken post-mortem from eight cases aged 20-76 years. Firstly, the regional distribution of GABA receptors and benzodiazepine receptors was studied using autoradiography following in vitro labelling of cryostat sections with tritiated ligands. This was followed by a detailed study of the cellular and subcellular distribution and localization of GABA and benzodiazepine/GABAA receptors by light and electron microscopy using immunohistochemical techniques with monoclonal antibodies to GABA and to the alpha and beta subunits of the benzodiazepine/GABAA receptor complex. The results showed a close correspondence in the regional distributions of GABA, GABA (GABAA and GABAB) receptors and benzodiazepine receptors. The highest density of GABA-like immunoreactivity, GABA receptors and benzodiazepine receptors was localized as a dense band within lamina II of the dorsal horn (especially inner lamina II) with moderately high densities in laminae I and III. The remaining laminae of the spinal gray matter showed much lower levels of labelling. A close correspondence was also seen in the distribution of GABA-like immunoreactivity and of benzodiazepine/GABAA receptor immunoreactivity at the cellular and subcellular levels. At the cellular level, the greatest number of GABA-immunoreactive cells was found in lamina II; they comprised small, round to oval cells and, on the basis of soma size, shape, orientation and dendromorphology, they corresponded to previously described islet and filamentous cells. Benzodiazepine/GABAA receptor immunoreactivity was also localized on the same cell types in lamina II. At the subcellular level in lamina II, GABA-immunoreactive axon terminals mainly established axodendritic synaptic contacts. Small numbers of GABA-immunoreactive axon terminals appear to form possible axo-axonic contacts in complex synaptic arrays. Benzodiazepine/GABAA receptors were localized within the same types of synaptic complexes in which GABA-immunoreactive axon terminals were found. In these synaptic complexes, benzodiazepine/GABAA receptor immunoreactivity was associated with presynaptic and postsynaptic membranes and on apparent non-synaptic membranes. These results show a high concentration of GABA, GABA receptors and benzodiazepine receptors in lamina II of the dorsal horn of the human spinal cord and suggest a possible role for GABA in spinal sensory functions.
authors.affiliation: Department of Anatomy, School of Medicine, University of Auckland, New Zealand.
authors.forename: H J
authors.initials: HJ
authors.lastname: Waldvogel
authors.forename: R L
authors.initials: RL
authors.lastname: Faull
authors.forename: K L
authors.initials: KL
authors.lastname: Jansen
authors.forename: M
authors.initials: M
authors.lastname: Dragunow
authors.forename: J G
authors.initials: JG
authors.lastname: Richards
authors.forename: H
authors.initials: H
authors.lastname: Mohler
authors.forename: P
authors.initials: P
authors.lastname: Streit
mesh_terms: D001345:Autoradiography; D005260:Female; D005445:Flunitrazepam / Q000378:metabolism*; D006801:Humans; D007124:Immunoenzyme Techniques; D008297:Male; D016253:Microscopy, Immunoelectron; D008875:Middle Aged; D011963:Receptors, GABA-A / Q000032:analysis* / Q000378:metabolism; D013116:Spinal Cord / Q000378:metabolism* / Q000473:pathology / Q000648:ultrastructure; D014316:Tritium; D005680:gamma-Aminobutyric Acid / Q000032:analysis / Q000378:metabolism*
chemical_list: D011963:Receptors, GABA-A; D014316:Tritium; D005680:gamma-Aminobutyric Acid; D005445:Flunitrazepam