Abstract
gamma-Aminobutyric acid (GABA) receptor/channel rho 1 subunits are important components in inhibitory pathways in the central nervous system. However, the precise locations and roles of these receptors in the central nervous system are unknown. We studied the expression localization of GABA receptor/channel rho 1 subunit in mouse spinal cord and dorsal root ganglia (DRG). The immunohistochemistry results indicated that GABA receptor/channel rho 1 subunits were expressed in mouse spinal cord superficial dorsal horn (lamina I and lamina II) and in DRG. To understand the functions of the GABA receptor/channel rho 1 subunit in these crucial sites of sensory transmission in vivo, we generated GABA receptor/channel rho 1 subunit mutant mice (rho 1-/-). GABA receptor/channel rho 1 subunit expression in the rho 1-/- mice was eliminated completely, whereas the gross neuroanatomical structures of the rho 1-/- mice spinal cord and DRG were unchanged. Electrophysiological recording showed that GABA-mediated spinal cord response was altered in the rho 1-/- mice. A decreased threshold for mechanical pain in the rho 1-/- mice compared with control mice was observed with the von Frey filament test. These findings indicate that the GABA receptor/channel rho 1 subunit plays an important role in modulating spinal cord pain transmission functions in vivo.
Highlights
␥-Aminobutyric acid (GABA)1 is the major inhibitory neurotransmitter in the vertebrate central nervous system (CNS)
GABA receptor/channel 1 subunit is highly enriched in the retina, where strong immunoreactivities of 1 and 2 subunits have been found in the inner plexiform layer, and weaker immunoreactivities have been found in the outer plexiform layer and cell bodies of bipolar cells [16, 17, 22]
Expression of GABA Receptor/Channel 1 Subunit in Spinal Cord and dorsal root ganglia (DRG)—Total RNA samples from mouse spinal cord, retina, and liver tissues were analyzed with RT-PCR using 1-specific primers
Summary
␥-Aminobutyric acid (GABA) is the major inhibitory neurotransmitter in the vertebrate central nervous system (CNS). GABAA receptor/channels are inhibited by bicuculline [1], GABAB receptors are sensitive to baclofen (an agonist) [2], whereas GABAC receptor/channels are insensitive to both bicuculline and baclofen [3, 4]. Recent evidence indicates that the 1 subunit is able to assemble with the GABAA receptor ␥2 subunit in the brain and spinal cord to form a novel hybrid GABA receptor/channel (19 –21). The GABAC receptor/channel formed by the 1 subunit is suggested to be a unique subclass of the GABA-gated ionotropic receptor/channel family. The functions of the GABA receptor/channel 1 subunit are mainly studied in the retina, where it is thought that the GABAC receptor/channel formed by the 1 subunit is involved in mediating lateral inhibition [30, 34] and local gain control circuitry [34, 35]. The functional significance of the GABA receptor/channel 1 subunit in the spinal sensory pathway remains to be resolved
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
