GABA-ACTIVATED CHLORIDE CURRENTS OF POSTNATAL MOUSE RETINAL GANGLION-CELLS ARE BLOCKED BY ACETYLCHOLINE AND ACETYLCARNITINE - HOW SPECIFIC ARE ION CHANNELS IN IMMATURE NEURONS

The goal of this study was to clarify pharmacological properties of GA BA(A) receptors in cells of the mouse retinal ganglion cell layer in s itu. Spontaneous synaptic currents and responses to exogenous GABA wer e recorded from individual neurons in retinal whole mounts (postnatal days 1-3) or retinal stripe preparations (postnatal days 4-6). Drugs w ere applied by a fast local superfusion system. Current responses were measured with the patch-clamp technique in the whole-cell configurati on. All cells responded to exogenous GABA (average EC(50) and Hill coe fficient: 16.7 mu M and 0.95 respectively) and generated GABAergic syn aptic currents in response to elevated KCl. GABA-induced currents of r etinal ganglion cells were blocked by bicuculline, picrotoxin and Zn2, as well as strychnine, and increased by pentobarbital, clonazepam an d 3 alpha-hydroxy-5 alpha-pregnan-20-one. In some retinal ganglion cel ls GABA caused an increase in the frequency of spontaneous synaptic cu rrents, which points to a partially depolarizing action of this tradit ionally inhibitory neurotransmitter in the neural retina. Our major ob servation is that acetylcholine and acetylcarnitine blocked or reduced GABAergic inhibitory postsynaptic currents and responses to exogenous GABA. This effect was seen in only a fraction of retinal ganglion cel ls and occurred in both the undesensitized and the desensitized state of the GABA(A) receptor. The block was voltage-independent and persist ed during coapplication with the nicotinic and muscarinic acetylcholin e receptor antagonists D-tubocurarine and atropine. In contrast to GAB A-activated Cl- currents, glycine-activated Cl- currents remained unaf fected by acetylcholine and acetylcarnitine. Acetylcarnitine had no ef fect on voltage-activated Ca2+ channel currents and glutamate-activate d currents. Similar results were obtained in a dissociated cell cultur e preparation from the neonatal rat superior colliculus. In these cell s acetylcholine induced a rightward shift in the dose-response curve f or GABA. Taken together, these results indicate that acetylcholine and acetylcarnitine can act directly at the GABA(A) binding site and ther eby reduce the action of GABA in the immature retina.