title: Tunicamycin decreases the probability of single-channel openings for N-methyl-D-aspartate and alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptors.
abstract: In whole-cell patches from cultured rat hippocampal neurons, tunicamycin (0.1-30 microM), an inhibitor of protein N-glycosylation, depressed currents through N-methyl-D-aspartate and alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptor channels in a concentration-dependent manner. Tunicamycin shifted the agonist concentration-response curve for each receptor type to the right. In an outside-out patch-clamp configuration, tunicamycin reduced the number of single-channel opening events in parallel with prolonged mean shut time, without affecting the slope conductance for both the receptors. These tunicamycin effects were obtained with acute treatment, suggesting an action independent of any blockage of N-glycosylation. Tunicamycin, thus, may modify the agonist binding affinity of N-methyl-D-aspartate and alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptors, thereby causing a decrease in the probability of single-channel openings leading to the depression of whole-cell membrane currents.
authors.affiliation: Department of Physiology, Hyogo College of Medicine, Nishinomiya, Japan.
authors.forename: Keishi
authors.initials: K
authors.lastname: Maruo
authors.forename: Satoshi
authors.initials: S
authors.lastname: Yamamoto
authors.forename: Takeshi
authors.initials: T
authors.lastname: Kanno
authors.forename: Takahiro
authors.initials: T
authors.lastname: Yaguchi
authors.forename: Soji
authors.initials: S
authors.lastname: Maruo
authors.forename: Shinichi
authors.initials: S
authors.lastname: Yashiya
authors.forename: Tomoyuki
authors.initials: T
authors.lastname: Nishizaki
mesh_terms: D015763:2-Amino-5-phosphonovalerate / Q000494:pharmacology; D000818:Animals; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D004307:Dose-Response Relationship, Radiation; D004347:Drug Interactions; D004558:Electric Stimulation / Q000379:methods; D004622:Embryo, Mammalian; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D006624:Hippocampus / Q000166:cytology; D015640:Ion Channel Gating / Q000187:drug effects*; D007608:Kainic Acid / Q000494:pharmacology; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology / Q000528:radiation effects; D016202:N-Methylaspartate / Q000494:pharmacology; D009474:Neurons / Q000187:drug effects*; D018408:Patch-Clamp Techniques / Q000379:methods; D011336:Probability; D011810:Quinoxalines / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D011930:Reaction Time / Q000187:drug effects; D018091:Receptors, AMPA / Q000502:physiology*; D016194:Receptors, N-Methyl-D-Aspartate / Q000502:physiology*; D014415:Tunicamycin / Q000494:pharmacology*
chemical_list: D018690:Excitatory Amino Acid Agonists; D018691:Excitatory Amino Acid Antagonists; D011810:Quinoxalines; D018091:Receptors, AMPA; D016194:Receptors, N-Methyl-D-Aspartate; D014415:Tunicamycin; C056723:FG 9041; D016202:N-Methylaspartate; D015763:2-Amino-5-phosphonovalerate; D007608:Kainic Acid