Multiple GABA receptor subtypes mediate inhibition of calcium influx at rat retinal bipolar cell terminals

Abstract

Inhibitory effects of GABA on K+-evoked Ca2+ influx into rat retinal bipolar cell terminals were studied using calcium imaging methods. Application of high K+ evokes a sustained, reversible increase in [Ca2+](i) at bipolar cell terminals, which occurs mainly via dihydropyridine-sensitive (L-type) Ca2+ channels. There are at least two GABA receptor subtypes coexisting at bipolar cell terminals: a conventional GABA(A) receptor and a bicuculline/baclofen-insensitive GABA receptor. Activation of either GABA receptor inhibited the K+-evoked Ca2+ response. However, these two GABA receptor subtypes have distinct properties. GABA(A) receptors suppress the Ca2+ response only at relatively high concentrations of agonist, and with fas+ kinetics and a narrow dynamic range. In contrast, the bicuculline/baclofen-insensitive GABA receptors produce inhibition on the Ca2+ response at a much lower concentration of agonist, and with slow onset and a wider dynamic range. The pharmacologic profile of the bicuculline/baclofen-insensitive GABA receptor at bipolar cell terminals is most similar to the GABA(c) receptor reported by Feigenspan et al. (1993). Unlike the GABA(c) receptors described in other species, it is extremely insensitive to picrotoxin. Therefore, it may be appropriate to refer to this receptor as a picrotoxin-insensitive GABA(c) receptor. 3- Aminopropyl(methyl)phosphinic acid (3-APMPA) and 3-aminopropylphosphonic (3- APA), two phosphate analogs of GABA, selectively antagonize the picrotoxin- insensitive GABA(c) receptors but not the GABA(A) receptors in this system. These results imply a functional role for multiple GABA receptors in regulating synaptic transmission at bipolar cell terminals.