Functional segregation of synaptic GABAA and GABAC 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 (tau(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 (gamma) 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 gamma is estimated to be 4 pS. Identified GABA(C) receptor mIPSCs exhibit a slow decay (tau(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.
Palmer
Mary J
MJ
Neuroscience Group, Institute for Science and Technology in Medicine, Keele University, Keele, ST5 5BG, UK. m.j.palmer@cns.keele.ac.uk
D000818:Animals; D002478:Cells, Cultured; D006054:Goldfish / Q000502:physiology*; D017729:Presynaptic Terminals / Q000502:physiology*; D018079:Receptors, GABA / Q000378:metabolism*; D011963:Receptors, GABA-A / Q000378:metabolism*; D051245:Retinal Bipolar Cells / Q000502:physiology*
C087200:GABA-C receptor; D018079:Receptors, GABA; D011963:Receptors, GABA-A