Different combinations of GABAA and GABAC receptors confer distinct temporal properties to retinal synaptic responses

This study addresses how gamma-aminobutyric acid-A (GABA(A)) and GABA(C) receptors confer distinct temporal properties to neuronal synaptic responses. The retina is a model system for the study of postsynaptic contributions to synaptic responses because GABAergic amacrine cells synapse onto neurons, which have different combinations of GABA(A), and GABA(C) receptors. It is not known, however, how GABA(A) versus GABA(C) receptors influence the time course of retinal synaptic responses or what proportion of inhibitory input is mediated by each receptor type. We examined the time courses of synaptic responses mediated by GABA receptors in ganglion and bipolar cells by recording currents evoked by activating amacrine cells with a stimulating electrode in the salamander retinal slice. The pharmacologically isolated, GABAergic synaptic currents were long-lasting in bipolar cells and relatively brief in ganglion cells. The receptors that mediated these temporally distinct synaptic responses exhibited different pharmacological properties. In ganglion cells, GABAergic synaptic currents were abolished by the GABA(A) receptor antagonists bicuculline or SR95531. In bipolar cells, the GABA(C) receptor antagonist 3-aminopropyl [methyl]phosphonic acid (3-APMPA) largely blocked GABAergic synaptic responses; the remaining response was blocked by bicuculline or SR95531. The GABA(A) receptor component of the bipolar cell response was relatively brief compared with the GABA(C) receptor component. Puffing GABA onto ganglion cell dendrites or bipolar cell terminals yielded similar pharmacological and kinetic results, indicating that transmitter release differences did not determine the response time courses. Moreover, the GABA(C) receptors on bipolar cells may be different from those reported in rat or fish retina because imidazole-4-acetic acid (I4AA), which acts as an antagonist in these preparations, acts as an agonist in salamander. Our data show that the prolonged synaptic responses in bipolar cells were mediated predominantly by GABA(C) receptors, whereas transient synaptic responses in ganglion cells were mediated by GABA(A) receptors.