title: Blocking AMPA receptor desensitization prolongs spontaneous EPSC decay times and depolarizes H1 horizontal cells in carp retinal slices.
abstract: Desensitization of H1 horizontal cell (H1 HC) glutamate receptors was investigated in carp retinal slices using cyclothiazide (CTZ), an inhibitor of AMPA receptor desensitization. 100 microM CTZ depolarized H1 HCs and increased the amplitude of light responses, without any prominent changes in their kinetics. Spontaneous EPSCs (sEPSCs) in H1 HCs were observed in the presence of 2.5 mM heptanol, an uncoupling agent of gap junctions. 20 microM GYKI52466 (an AMPA receptor antagonist) blocked the sEPSCs, consistent with the sEPSCs being mediated by AMPA receptors. 100 microM cobalt suppressed the frequency of sEPSCs without changing their mean peak amplitude, suggesting that calcium-dependent transmitter release from cones was not affected by heptanol. CTZ increased the total inward charge transferred per sEPSC by increasing the sEPSC decay time constant twofold, without any significant change in their frequency and mean peak amplitude. This suggests that the depolarizing effect of CTZ on H1 HCs was due to blocking desensitization of AMPA receptors, increasing the inward current induced by glutamate released from cone synaptic terminals. The desensitization of glutamate receptors may function to extend the dynamic range of H1 HC light responses.
authors.affiliation: Supermolecular Division, Electrotechnical Laboratory, Tsukuba, Ibaraki 305-8568, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Hirasawa
authors.forename: R
authors.initials: R
authors.lastname: Shiells
authors.forename: M
authors.initials: M
authors.lastname: Yamada
mesh_terms: D000818:Animals; D001581:Benzothiadiazines / Q000494:pharmacology; D002347:Carps / Q000033:anatomy & histology / Q000378:metabolism*; D004232:Diuretics; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects / Q000502:physiology*; D019850:Heptanol / Q000494:pharmacology; D007395:Interneurons / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology*; D009924:Organ Culture Techniques; D020419:Photoreceptor Cells, Vertebrate / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D018091:Receptors, AMPA / Q000187:drug effects / Q000378:metabolism*; D012160:Retina / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D049993:Sodium Chloride Symporter Inhibitors / Q000494:pharmacology; D013569:Synapses / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure; D013997:Time Factors; D014785:Vision, Ocular / Q000187:drug effects / Q000502:physiology
chemical_list: D001581:Benzothiadiazines; D004232:Diuretics; D018091:Receptors, AMPA; D049993:Sodium Chloride Symporter Inhibitors; D019850:Heptanol; C004639:cyclothiazide