Distribution and depression of the GABA B receptor in the spinal dorsal horn of adult rat

Abstract

γ-Aminobutyric acid (GABA) is a principal inhibitory neurotransmitter in vertebrate nervous system. The metabotropic receptor for GABA, GABA B receptor, is characterized as a G protein-coupled receptor subtype. In the present study, GABA B receptor-like immunoreactivity (GABA BR-LI) in the rat spinal cord and dorsal root ganglion (DRG), as well as GABA B receptor-mediated depression in the spinal dorsal horn were examined by using immunohistochemistry and whole-cell voltage-clamp recording technique, respectively. Under light microscope, GABA BR-LI was densely found in laminae I and II of the dorsal horn. DRG cells of various diameters also showed GABA BR-LI. Electron microscopy further revealed that GABA BR-LI was also localized in terminals of myelinated, unmyelinated fibers as well as the somatodendritic sites of dorsal horn neurons. Bath application of a GABA B receptor agonist, baclofen (10 μM, 30 s), induced a slow outward (inhibitory) current in dorsal horn neurons. This slow current was depressed when the postsynaptic G protein-coupled receptor was inhibited, indicating the postsynaptic action of baclofen. Under the condition of postsynaptic GABA B receptor being inhibited, baclofen (10 μM, 60 s) depressed large (Aβ) and fine (C, Aδ) afferent fiber-evoked monosynaptic excitatory postsynaptic currents, indicating presynaptic inhibition of GABA B receptor on elicited neurotransmitter release. Taken together, the results suggest that baclofen-sensitive GABA B receptor is expressed pre- and postsynaptically on primary afferent fibers and neurons in the spinal dorsal horn; activation of GABA B receptor in the dorsal horn postsynaptically hyperpolarizes dorsal horn neurons and presynaptically inhibits primary afferents.