title: Characterization of the glycinergic input to bipolar cells of the mouse retina.
abstract: Glycine and gamma-aminobutyric acid (GABA) are the major inhibitory transmitters of the mammalian retina, and bipolar cells receive GABAergic and glycinergic inhibition from multiple amacrine cell types. Here we evaluated the functional properties and subunit composition of glycine receptors (GlyRs) in bipolar cells. Patch-clamp recordings were performed from retinal slices of wild-type, GlyRalpha1-deficient (Glra1(spd-ot)) and GlyRalpha3-deficient (Glra3(-/-)) mice. Whole-cell currents following glycine application and spontaneous inhibitory postsynaptic currents (IPSCs) were analysed. During the recordings the cells were filled with Alexa 488 and, thus, unequivocally identified. Glycine-induced currents of bipolar cells were picrotoxinin-insensitive and thus represent heteromeric channels composed of alpha and beta subunits. Glycine-induced currents and IPSCs were absent from all bipolar cells of Glra1(spd-ot) mice, indicating that GlyRalpha1 is an essential subunit of bipolar cell GlyRs. By comparing IPSCs of bipolar cells in wild-type and Glra3(-/-) mice, no statistically significant differences were found. OFF-cone bipolar (CB) cells receive a strong glycinergic input from AII amacrine cells, that is preferentially based on the fast alpha1beta-containing channels (mean decay time constant tau = 5.9 +/- 1.4 ms). We did not observe glycinergic IPSCs in ON-CB cells and could elicit only small, if any, glycinergic currents. Rod bipolar cells receive a prominent glycinergic input that is mainly mediated by alpha1beta-containing channels (tau = 5.5 +/- 1.6 ms). Slow IPSCs, the characteristic of GlyRs containing the alpha2 subunit, were not observed in bipolar cells. Thus, different bipolar cell types receive kinetically fast glycinergic inputs, preferentially mediated by GlyRs composed of alpha1 and beta subunits.
authors.affiliation: Department Neuroanatomy, Max-Planck-Institute for Brain Research, Frankfurt/Main, Germany.
authors.forename: Elena
authors.initials: E
authors.lastname: Ivanova
authors.forename: Ulrike
authors.initials: U
authors.lastname: Müller
authors.forename: Heinz
authors.initials: H
authors.lastname: Wässle
mesh_terms: D000818:Animals; D004307:Dose-Response Relationship, Radiation; D004347:Drug Interactions; D004558:Electric Stimulation / Q000379:methods; D018756:GABA Antagonists / Q000494:pharmacology; D005998:Glycine / Q000494:pharmacology*; D018684:Glycine Agents / Q000494:pharmacology; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D007150:Immunohistochemistry / Q000379:methods; D066298:In Vitro Techniques; D016256:Lewis X Antigen / Q000378:metabolism; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology / Q000528:radiation effects; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009433:Neural Inhibition / Q000187:drug effects* / Q000502:physiology / Q000528:radiation effects; D009474:Neurons / Q000187:drug effects* / Q000502:physiology / Q000528:radiation effects; D018408:Patch-Clamp Techniques / Q000379:methods; D010721:Phosphinic Acids / Q000494:pharmacology; D051571:Protein Kinase C-alpha / Q000378:metabolism; D011724:Pyridazines / Q000494:pharmacology; D011725:Pyridines / Q000494:pharmacology; D018009:Receptors, Glycine / Q000378:metabolism; D012160:Retina / Q000166:cytology*; D013331:Strychnine / Q000494:pharmacology; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology* / Q000528:radiation effects; D013997:Time Factors; D015293:Transducin / Q000235:genetics / Q000378:metabolism; D005680:gamma-Aminobutyric Acid / Q000494:pharmacology
chemical_list: C101879:(1,2,5,6-tetrahydropyridin-4-yl)methylphosphinic acid; D018756:GABA Antagonists; D018684:Glycine Agents; D016256:Lewis X Antigen; D010721:Phosphinic Acids; D011724:Pyridazines; D011725:Pyridines; D018009:Receptors, Glycine; C113965:glycine receptor alpha3 subunit; D049452:Green Fluorescent Proteins; C075192:gustducin; D005680:gamma-Aminobutyric Acid; C049853:gabazine; D051571:Protein Kinase C-alpha; D015293:Transducin; D013331:Strychnine; D005998:Glycine