Inhibition is crucial for normal function in the nervous system. In the CNS, inhibition is mediated primarily by the amino acid GABA via activation of two ionotropic GABA receptors, GABAA and GABAC. GABA A receptor composition and function have been well characterized, whereas much less is known about native GABAC receptors, Differences in molecular composition, anatomical distributions, and physiological properties strongly suggest that GABAA receptors and GABA C receptors have distinct functional roles in the CNS. To determine the functional role of GABAC receptors, we eliminated their expression in mice using a knock-out strategy. Although native rodent GABA C receptors are composed of ρ1 and ρ2 subunits, we show that after ρ1 subunit expression was selectively eliminated there was no GABAC receptor expression. We assessed GABAC receptor function in the retina because GABAC receptors are highly expressed on the axon terminals of rod bipolar cells and because this site modulates the visual signal to amacrine and ganglion cells. In GABACρ1 null mice, GABA-evoked responses, normally mediated by GABAC receptors, were eliminated, and signaling from rod bipolar cells to third order cells was altered. These data demonstrate that elimination of the GABACρ1 subunit, via gene targeting, results in the absence of GABAC receptors in the retina and selective alterations in normal visual processing.
|Number of pages||12|
|Journal||Journal of Neuroscience|
|State||Published - May 15 2002|
- Chloride channel
- Ionotropic receptor
- Rod bipolar cell
- Whole-cell patch clamp