GABAC receptors on ferret retinal bipolar cells: a diversity of subtypes in mammals?

The GABAC receptor subtypes on bipolar cells of rats and cold-blooded vertebrates differ in their pharmacological properties and probably have different molecular compositions. With the exception of the rat, native GABAC receptors in mammals had not been studied. In ferret, whole-cell, voltage-clamp recordings were made from bipolar cells in the retinal slice preparation to determine which subtype of GABAC receptor predominated. Puff-evoked GABA currents in bipolar cells were partially reduced by the GABAA receptor antagonist bicuculline, indicating that both GABAA and GABAC receptors mediated the responses. By contrast, GABA currents of ganglion cells were always completely blocked by bicuculline, indicating that GABAA receptors predominated on these cells. Small-amplitude GABA currents of bipolar cells evoked by short-duration puffs were less sensitive to bicuculline than large-amplitude currents evoked by long-duration puffs. This indicates that GABAC receptors mediated proportionately more of the small-amplitude, puff-evoked responses and GABAA receptors mediated more of the large-amplitude, puff-evoked responses. In bipolar cells, the bicuculline-resistant component of the GABA current was entirely blocked by 3-APMPA (3-aminopropyl-(methyl)phosphonic acid), a GABAC receptor antagonist. Picrotoxin, which is relatively ineffective at rat GABAC receptors, completely blocked GABA currents in ferret bipolar cells, indicating that GABAC receptors on ferret bipolar cells resemble those in lower vertebrates rather than those in the rat retina. These results suggest that there may be a diversity of GABAC receptor subtypes on mammalian bipolar cells.