A novel GABA receptor modulates synaptic transmission from bipolar to ganglion and amacrine cells in the tiger salamander retina

Abstract

We investigated the mechanisms underlying the modulation of transmitter release from bipolar cells. Three currents, measured under whole-cell patch clamp in the tiger salamander retinal slice, were used to identify the sites of modulation and to establish their pharmacological profile. (1) A light-elicited inhibitory current was measured in bipolar cells that could be blocked by picrotoxin. This input probably arrives via GABAergic amacrine cells since there is high GABA sensitivity at the bipolar cell terminals and little GABA sensitivity at the dendrites. (2) Voltage-gated barium currents were elicited by depolarizing voltage ramps in bipolar cells. These currents most likely flowed through the calcium channels that are associated with transmitter release at the bipolar terminal. Bath-applied GABA suppressed the barium currents. (3) Puffs of potassium at bipolar dendrites depolarized bipolar cells and elicited an excitatory synaptic current measured in amacrine and ganglion cells. The excitatory synaptic currents, which reflect bipolar cell transmitter release, were also blocked by bath-applied GABA. For all three currents, the effects of GABA could be reversed by picrotoxin, but not by bicuculline or SR95531. The pharmacological profile of the receptors mediating GABA suppression of the barium currents and of excitatory synaptic transmission is characteristic of GABAC receptors (Cutting et al., 1991; Polenzani et al., 1991; Shimada et al., 1992). GABA receptors at bipolar terminals gate a chloride conductance, and most were found to have the pharmacological properties of GABAC receptors (Lukasiewicz et al., 1994). By contrast, the GABA receptors on ganglion cells have been found to be the GABAA subtype (Lukasiewicz and Werblin, 1990; Lukasiewicz et al., 1994). These results suggest that GABA acts presynaptically at GABAC receptors at the bipolar cell terminals. The GABAC receptors open chloride channels that can modulate the release of excitatory transmitter. In some experiments, bicuculline or SR95531 reversed a component of the GABA suppression of synaptic transmission. This indicates that GABAA receptors may also play a role in modulating transmission between bipolar and ganglion cells.