title: Group III metabotropic glutamate receptors and exocytosed protons inhibit L-type calcium currents in cones but not in rods.
abstract: Light responses of photoreceptors (rods and cones) are transmitted to the second-order neurons (bipolar cells and horizontal cells) via glutamatergic synapses located in the outer plexiform layer of the retina. Although it has been well established that postsynaptic group III metabotropic glutamate receptors (mGluRs) of ON bipolar cells contribute to generating the ON signal, presynaptic roles of group III mGluRs remain to be elucidated at this synaptic connection. We addressed this issue by applying the slice patch-clamp technique to the newt retina. OFF bipolar cells and horizontal cells generate a steady inward current in the dark and a transient inward current at light offset, both of which are mediated via postsynaptic non-NMDA receptors. A group III mGluR-specific agonist, L-2-amino-4-phosphonobutyric acid (L-AP-4), inhibited both the steady and off-transient inward currents but did not affect the glutamate-induced current in these postsynaptic neurons. L-AP-4 inhibited the presynaptic L-type calcium current (ICa) in cones by shifting the voltage dependence of activation to more positive membrane potentials. The inhibition of ICa was most prominent around the physiological range of cone membrane potentials. In contrast, L-AP-4 did not affect L-type ICa in rods. Paired recordings from photoreceptors and the synaptically connected second-order neurons confirmed that L-AP-4 inhibited both ICa and glutamate release in cones but not in rods. Furthermore, we found that exocytosed protons also inhibited ICa in cones but not in rods. Selective modulation of ICa in cones may help broaden the dynamic range of synaptic transfer by controlling the amount of transmitter release from cones.
authors.affiliation: Department of Psychology, Graduate School of Humanities and Sociology, The University of Tokyo, Tokyo 113-0033, Japan.
authors.forename: Nobutake
authors.initials: N
authors.lastname: Hosoi
authors.forename: Itaru
authors.initials: I
authors.lastname: Arai
authors.forename: Masao
authors.initials: M
authors.lastname: Tachibana
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism; D020746:Calcium Channels, L-Type / Q000502:physiology*; D004347:Drug Interactions; D004558:Electric Stimulation / Q000379:methods; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects / Q000502:physiology / Q000528:radiation effects; D018698:Glutamic Acid / Q000494:pharmacology; D006153:Guanosine Diphosphate / Q000031:analogs & derivatives / Q000494:pharmacology; D006531:HEPES / Q000494:pharmacology; D066298:In Vitro Techniques; D008027:Light; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology / Q000528:radiation effects; D009433:Neural Inhibition / Q000187:drug effects / Q000502:physiology* / Q000528:radiation effects; D009474:Neurons / Q000187:drug effects; D018408:Patch-Clamp Techniques / Q000379:methods; D011422:Propionates / Q000494:pharmacology; D011522:Protons; D011810:Quinoxalines / Q000494:pharmacology; D018091:Receptors, AMPA / Q000502:physiology*; D012160:Retina / Q000166:cytology*; D017949:Retinal Cone Photoreceptor Cells / Q000187:drug effects* / Q000378:metabolism; D017948:Retinal Rod Photoreceptor Cells / Q000187:drug effects / Q000378:metabolism; D012455:Salamandridae; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology / Q000528:radiation effects; D013873:Thionucleotides / Q000494:pharmacology; D014785:Vision, Ocular / Q000187:drug effects / Q000502:physiology / Q000528:radiation effects; D014795:Visual Pathways / Q000187:drug effects
chemical_list: C114785:2-amino-4-phosphono-propinate; D020746:Calcium Channels, L-Type; D018690:Excitatory Amino Acid Agonists; D018691:Excitatory Amino Acid Antagonists; D011422:Propionates; D011522:Protons; D011810:Quinoxalines; D018091:Receptors, AMPA; D013873:Thionucleotides; C104723:glutamate receptor ionotropic, AMPA 3; C062865:2,3-dioxo-6-nitro-7-sulfamoylbenzo(f)quinoxaline; D006153:Guanosine Diphosphate; D018698:Glutamic Acid; C023427:guanosine 5'-O-(2-thiodiphosphate); D006531:HEPES; D002118:Calcium