NOVEL GABA RESPONSES FROM ROD-DRIVEN RETINAL HORIZONTAL CELLS

Gamma-AMINOBUTYRIC acid (GABA) is the main inhibitory neurotransmitter in the central nervous system. Two classes of GABA receptors (GABA(A) and GABA(B)) have been identified. GABA(A) receptors are ligand-gated chloride channels that are competitively antagonized by bicuculline, noncompetitively blocked by picrotoxin, and often allosterically modulated by barbiturates and benzodiazepines1-3. GABA(B) receptors regulate potassium and calcium channels through G-protein and intracellular second-messenger pathways2,3, are selectively activated by baclofen, and are antagonized by phaclofen and 2-hydroxysaclofen4,5. For some years, evidence has accumulated that there are GABA receptors, especially prominent along visual pathways, which are neither antagonized by bicuculline nor activated by baclofen, but are activated by certain conformationally restricted analogues of GABA, including cis-4-aminocrotonic acid (CACA)6-9. These receptors have been designated GABA(C) receptors9. As yet, membrane current responses from isolated neurons that reflect this novel pharmacology have not been reported, although such responses have been recorded from oocytes injected with retinal messenger RNA10-13. Here we describe a chloride-mediated current response from isolated rod-driven horizontal cells (H4) of the white perch retina that has this novel pharmacology.