A NOVEL GABA RECEPTOR MODULATES SYNAPTIC TRANSMISSION FROM BIPOLAR TOGANGLION AND AMACRINE CELLS IN THE TIGER SALAMANDER RETINA

We investigated the mechanisms underlying the modulation of transmitte r release from bipolar cells. Three currents, measured under whole-cel l patch clamp in the tiger salamander retinal slice, were used to iden tify the sites of modulation and to establish their pharmacological pr ofile. (1) A light-elicited inhibitory current was measured in bipolar cells that could be blocked by picrotoxin. This input probably arrive s via GABAergic amacrine cells since there is high GABA sensitivity at the bipolar cell terminals and little GABA sensitivity at the dendrit es. (2) Voltage-gated barium currents were elicited by depolarizing vo ltage ramps in bipolar cells. These currents most likely flowed throug h the calcium channels that are associated with transmitter release at the bipolar terminal. Bath-applied GABA suppressed the barium current s. (3) Puffs of potassium at bipolar dendrites depolarized bipolar cel ls and elicited an excitatory synaptic current measured in amacrine an d ganglion cells. The excitatory synaptic currents, which reflect bipo lar cell transmitter release, were also blocked by bath-applied GABA. For all three currents, the effects of GABA could be reversed by picro toxin, 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 GABA(C) rece ptors (Cutting et al., 1991; Polenzani et al., 1991; Shimada et al., 1 992). GABA receptors at bipolar terminals gate a chloride conductance, and most were found to have the pharmacological properties of GABA(C) receptors (Lukasiewicz et al., 1994). By contrast, the GABA receptors on ganglion cells have been found to be the GABA(A) subtype (Lukasiew icz and Werblin, 1990; Lukasiewicz et al., 1994). These results sugges t that GABA acts presynaptically at GABA(C) receptors at the bipolar c ell terminals. The GABA(C) receptors open chloride channels that can m odulate the release of excitatory transmitter. In some experiments, bi cuculline or SR95531 reversed a component of the GABA suppression of s ynaptic transmission. This indicates that GABA(A) receptors may also p lay a role in modulating transmission between bipolar and ganglion cel ls.