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 GABAA receptors in cells of the mouse retinal ganglion cell layer in situ. Spontaneous synaptic currents and responses to exogenous GABA were recorded from individual neurons in retinal whole mounts (postnatal days 1-3) or retinal stripe preparations (postnatal days 4-6). Drugs were applied by a fast local superfusion system. Current responses were measured with the patch-clamp technique in the whole-cell configuration. All cells responded to exogenous GABA (average EC50 and Hill coefficient: 16.7 microM and 0.95 respectively) and generated GABAergic synaptic currents in response to elevated KCl. GABA-induced currents of retinal ganglion cells were blocked by bicuculline, picrotoxin and Zn2+, as well as strychnine, and increased by pentobarbital, clonazepam and 3 alpha-hydroxy-5 alpha-pregnan-20-one. In some retinal ganglion cells GABA caused an increase in the frequency of spontaneous synaptic currents, which points to a partially depolarizing action of this traditionally inhibitory neurotransmitter in the neural retina. Our major observation 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 cells and occurred in both the undesensitized and the desensitized state of the GABAA receptor. The block was voltage-independent and persisted during coapplication with the nicotinic and muscarinic acetylcholine receptor antagonists D-tubocurarine and atropine. In contrast to GABA-activated Cl- currents, glycine-activated Cl- currents remained unaffected by acetylcholine and acetylcarnitine.(ABSTRACT TRUNCATED AT 250 WORDS)
Department of Neurophysiology, Max Planck Institute for Psychiatry, Martinsried, FRG.
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Bähring
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Standhardt
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Martelli
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Grantyn
D000108:Acetylcarnitine / Q000494:pharmacology*; D000109:Acetylcholine / Q000494:pharmacology*; D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D001640:Bicuculline / Q000494:pharmacology; D018118:Chloride Channels / Q000187:drug effects*; D002998:Clonazepam / Q000494:pharmacology; D018756:GABA Antagonists / Q000494:pharmacology*; D005998:Glycine / Q000494:pharmacology; D051379:Mice; D008810:Mice, Inbred C57BL; D009474:Neurons / Q000187:drug effects; D018408:Patch-Clamp Techniques; D010424:Pentobarbital / Q000494:pharmacology; D010852:Picrotoxin / Q000494:pharmacology; D011189:Potassium Chloride / Q000494:pharmacology; D011280:Pregnanolone / Q000494:pharmacology; D011810:Quinoxalines / Q000494:pharmacology; D012160:Retina / Q000166:cytology / Q000254:growth & development*; D012165:Retinal Ganglion Cells / Q000187:drug effects* / Q000502:physiology; D013331:Strychnine / Q000494:pharmacology; D013379:Substrate Specificity; D013779:Tetrodotoxin / Q000494:pharmacology; D015032:Zinc / Q000494:pharmacology; D005680:gamma-Aminobutyric Acid / Q000494:pharmacology*
D000108:Acetylcarnitine; D000109:Acetylcholine; D001640:Bicuculline; D018118:Chloride Channels; D002998:Clonazepam; D018756:GABA Antagonists; D005998:Glycine; D010424:Pentobarbital; D010852:Picrotoxin; D011189:Potassium Chloride; D011280:Pregnanolone; D011810:Quinoxalines; D013331:Strychnine; D013779:Tetrodotoxin; D015032:Zinc; D005680:gamma-Aminobutyric Acid; C056723:FG 9041