LIGAND-GATED CURRENTS OF ALPHA-GANGLION-CELLS AND BETA-GANGLION-CELLSIN THE CAT RETINAL SLICE

1. We studied the receptor pharmacology of the ligand-gated currents o f ON- and OFF- alpha and beta ganglion cells in a cat retinal slice pr eparation using the whole cell recording variation of the patch-clamp technique. Cat retinal slices were cut in N-2-hydroxyethylpiperazine-N '-2-ethanesulfonic acid (HEPES) buffer and incubated in a bicarbonate- buffered solution. Ganglion cells were voltage clamped at -70 mV in HE PES-buffered Ringer solution. The pipette solution contained a low con centration of Cl- to distinguish mixed cationic from Cl--mediated cond uctances, and Lucifer yellow (0.5%) was included for identification of the cell type. 2. In Ringer solution containing 1.2 mM Mg2+, current- voltage (I- V) curves of responses to the excitatory amino acid agonis t (EAA) N-methyl-D-aspartate (NMDA) (200 mu M) revealed a J-shaped fun ction. In Mg2+-free Ringer solution containing 200 mu M Cd2+ to block synaptic transmission, NMDA (200 mu M) elicited an inward current 5-8 times larger at -70 mV. In both conditions I-V curves of the NMDA-indu ced currents reversed near 0 mV. These results suggest that there are NMDA EAA receptors present directly on the dendrites of alpha and beta ganglion cells. Responses to NMDA were blocked by +/-2-amino-7-phosph onoheptanoic acid (AP7) (200 mu M). 3. In Ringer solution containing 2 00-1,000 mu M Cd2+ to block synaptic transmission, both ON- and OFF- a lpha and beta cells responded to kainic acid (10-50 mu M), pha-amino-3 -hydroxy-5-methylisoxazole-4-proprionic acid (AMPA) (20-70 mu M), and quisqualic acid (0.1-30 mu M) with inward currents that reversed near 0 mV. These responses were blocked by the quinoxaline EAA antagonist 6 -cyano-7-nitroquinoxaline-2,3-dione (CNQX) (10 mu M). The metabotropic agonists 1-aminocyclopentane-1,3-dicarboxylic acid (ACPD) (25 mu M) a nd L-2-amino-4-phosphonobutyric acid (L-APB) (50 mu M) in the presence of Cd2+ evoked little or no response for all cells tested. 4. In the presence of Cd2+, alpha and beta cells responded to gamma-aminobutyric acid (GABA) (200 mu M) and glycine (200 mu M) with inward currents th at reversed near -35 mV, the calculated chloride equilibrium potential E(cl). Responses to GABA and glycine were both strongly desensitizing . (+)Bicuculline methyl chloride (20 mu M) blocked an average of 90% o f the inward current evoked by 200 mu M GABA on all ganglion cell type s. Baclofen (10-100 mu M) had no effect on resting currents or on volt age-gated Ca2+ currents. Strychnine (1 mu M) blocked glycine-evoked cu rrents by an average of 94%. 5. We conclude that the excitatory and in hibitory ionotropic amino acid receptors present on ON- and OFF- alpha and beta cells are very similar. This suggests that some of the diffe rences observed in the response properties of these cells may be due t o different properties of their presynaptic inputs or differences in t heir voltage-gated channels.