title: Intracellular calcium release resulting from mGluR1 receptor activation modulates GABAA currents in wide-field retinal amacrine cells: a study with caffeine.
abstract: The modulatory action of calcium (Ca2+) released from intracellular stores on GABAA receptor-mediated current was investigated in wide-field amacrine cells isolated from the teleost, Morone chrysops, retina. Caffeine, ryanodine or inositol 1,4,5-triphosphate (IP3) markedly inhibited the GABAA current by elevating [Ca2+]i. The inhibition resulted from the activation of a Ca2+--> Ca2+/calmodulin --> calcineurin cascade. Long (>12 s) exposure to glutamate mimicked the caffeine effect, i.e. it inhibited the GABAA current by elevating [Ca2+]i through mGluR1 receptor activation and consequent IP3 generation. This pathway provides a 'timed' disinhibitory mechanism to potentiate excitatory postsynaptic potentials in wide-field amacrine cells. It occurs as a result of the suppression of GABA-mediated conductances as a function of the duration of presynaptic excitatory input activity. This is much like some forms of long-term potentiation in the central nervous system. In a local retinal circuit this will selectively accentuate particular excitatory inputs to the wide-field amacrine cell. Similar to other neural systems, we suggest that activity-dependent postsynaptic disinhibition is an important feature of the signal processing in the inner retina.
authors.affiliation: Dept. of Ophthalmology and Visual Sciences, John Moran Eye Center, University of Utah, Health Sciences Center, Salt Lake City, UT 84132, USA.
authors.forename: Jozsef
authors.initials: J
authors.lastname: Vigh
authors.forename: Eric M
authors.initials: EM
authors.lastname: Lasater
mesh_terms: D025042:Amacrine Cells / Q000187:drug effects* / Q000502:physiology; D000818:Animals; D000925:Anticoagulants / Q000494:pharmacology; D001640:Bicuculline / Q000494:pharmacology; D002110:Caffeine / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism*; D015220:Calcium Channels / Q000378:metabolism; D002347:Carps; D002478:Cells, Cultured; D000697:Central Nervous System Stimulants / Q000494:pharmacology*; D002614:Chelating Agents / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D004533:Egtazic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology; D004553:Electric Conductivity; D004791:Enzyme Inhibitors / Q000494:pharmacology; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology; D005110:Extracellular Space / Q000378:metabolism; D018756:GABA Antagonists / Q000494:pharmacology; D018698:Glutamic Acid / Q000502:physiology; D006493:Heparin / Q000494:pharmacology; D007150:Immunohistochemistry; D015544:Inositol 1,4,5-Trisphosphate / Q000494:pharmacology; D053496:Inositol 1,4,5-Trisphosphate Receptors; D007608:Kainic Acid / Q000494:pharmacology; D008564:Membrane Potentials / Q000187:drug effects; D008734:Methoxyhydroxyphenylglycol / Q000031:analogs & derivatives* / Q000494:pharmacology; D009943:Organophosphorus Compounds / Q000494:pharmacology; D018408:Patch-Clamp Techniques / Q000379:methods; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism; D011963:Receptors, GABA-A / Q000502:physiology*; D018094:Receptors, Metabotropic Glutamate / Q000037:antagonists & inhibitors / Q000378:metabolism*; D012160:Retina / Q000166:cytology*; D012433:Ryanodine / Q000494:pharmacology; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid / Q000494:pharmacology; D005680:gamma-Aminobutyric Acid / Q000494:pharmacology
chemical_list: D000925:Anticoagulants; D015220:Calcium Channels; D000697:Central Nervous System Stimulants; D002614:Chelating Agents; D004791:Enzyme Inhibitors; D018690:Excitatory Amino Acid Agonists; D018756:GABA Antagonists; D053496:Inositol 1,4,5-Trisphosphate Receptors; D009943:Organophosphorus Compounds; D018160:Receptors, Cytoplasmic and Nuclear; D011963:Receptors, GABA-A; D018094:Receptors, Metabotropic Glutamate; C104077:metabotropic glutamate receptor type 1; C068457:3-aminopropyl(methyl)phosphinic acid; D012433:Ryanodine; D002110:Caffeine; D018698:Glutamic Acid; D004533:Egtazic Acid; D008734:Methoxyhydroxyphenylglycol; D005680:gamma-Aminobutyric Acid; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid; D015544:Inositol 1,4,5-Trisphosphate; D006493:Heparin; C025603:1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid; D007608:Kainic Acid; D002118:Calcium; C010117:3,4-dihydroxyphenylglycol; D001640:Bicuculline