Functional segregation of synaptic GABA A and GABA C receptors in goldfish bipolar cell terminals

The transmission of light responses to retinal ganglion cells is regulated by inhibitory input from amacrine cells to bipolar cell (BC) synaptic terminals. GABA A and GABA C receptors in BC terminals mediate currents with different kinetics and are likely to have distinct functions in limiting BC output; however, the synaptic properties and localization of the receptors are currently poorly understood. By recording endogenous GABA receptor currents directly from BC terminals in goldfish retinal slices, I show that spontaneous GABA release activates rapid GABA A receptor miniature inhibitory postsynaptic currents (mIPSCs) (predominant decay time constant (τ decay ), 1.0 ms) in addition to a tonic GABA C receptor current. The GABA C receptor antagonist (1,2,5,6‐tetrahydropyridin‐4‐yl)methylphosphinic acid (TPMPA) has no effect on the amplitude or kinetics of the rapid GABA A mIPSCs. In addition, inhibition of the GAT‐1 GABA transporter, which strongly regulates GABA C receptor currents in BC terminals, fails to reveal a GABA C component in the mIPSCs. These data suggest that GABA A and GABA C receptors are highly unlikely to be synaptically colocalized. Using non‐stationary noise analysis of the mIPSCs, I estimate that GABA A receptors in BC terminals have a single‐channel conductance (γ) of 17 pS and that an average of just seven receptors mediates a quantal event. From noise analysis of the tonic current, GABA C receptor γ is estimated to be 4 pS. Identified GABA C receptor mIPSCs exhibit a slow decay (τ decay , 54 ms) and are mediated by approximately 42 receptors. The distinct properties and localization of synaptic GABA A and GABA C receptors in BC terminals are likely to facilitate their specific roles in regulating the transmission of light responses in the retina.