Novel GABA responses from rod- driven retinal horizontal cells

Abstract

γ-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 ligandgated chloride channels that are competitively antagonized by bicuculline, noncompetitively blocked by picrotoxin, and often allosterically modulated by barbiturates and benzodiazepines^1–3. GABA_B receptors regulate potassium and calcium channels through G-protein and intra-cellular second-messenger pathways^2,3, are selectively activated by baclofen, and are antagonized by phaclofen and 2-hydroxysaclofen^4,5. 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 RNA^10–13. Here we describe a chloridemediated current response from isolated rod-driven horizontal cells (H4) of the white perch retina that has this novel pharmacology.