GABA(C) RECEPTORS ON FERRET RETINAL BIPOLAR CELLS - A DIVERSITY OF SUBTYPES IN MAMMALS

The GABA(C) receptor subtypes on bipolar cells of rats and cold-bloode d vertebrates differ in their pharmacological properties and probably have different molecular compositions. With the exception of the rat, native GABA(C) receptors in mammals had not been studied. In ferret, w hole-cell, voltage-clamp recordings were made from bipolar cells in th e retinal slice preparation to determine which subtype of GABA(C) rece ptor predominated. Puff-evoked GABA currents in bipolar cells were par tially reduced by the GABAA receptor antagonist bicuculline, indicatin g that both GABAA and GABA(C) receptors mediated the responses. By con trast, GABA(A) currents of ganglion cells were always completely block ed by bicuculline, indicating that GABA(A) receptors predominated on t hese cells. Small-amplitude GABA currents of bipolar cells evoked by s hort-duration puffs were less sensitive to bicuculline than large-ampl itude currents evoked by long-duration puffs. This indicates that GABA (C) receptors mediated proportionately more of the small-amplitude, pu ff-evoked responses and GABA(A) receptors mediated more of the large-a mplitude, puff-evoked responses. In bipolar cells, the bicuculline-res istant component of the GABA current was entirely blocked by 3-APMPA(3 -aminopropyl-(methyl)phosphonic acid), a GABA(C) receptor antagonist. Picrotoxin, which is relatively ineffective at rat GABA(C) receptors, completely blocked GABA currents in ferret bipolar cells, indicating t hat GABA(C) 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 GABA(C) receptor subtypes on mammali an bipolar cells.