Tunicamycin inhibits NMDA and AMPA receptor responses independently of N-glycosylation.
In a whole-cell patch-clamp configuration, currents through N-methyl-D-aspartate (NMDA) and alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) receptor channels were monitored in cultured rat hippocampal neurons, and those currents were depressed to 25 and 28% of basal levels, respectively, by 3-min treatment with tunicamycin (10 microM), an inhibitor of protein N-glycosylation. Tunicamycin (10 microM) reduced amplitude of population spikes elicited in the dentate gyrus of rat hippocampal slices, reaching 78% of basal levels 60 min after the beginning of treatment, and long-term potentiation (LTP) of the perforant path was never induced in the presence of tunicamycin. Tunicamycin, thus, appears to serve as a modulator for NMDA and AMPA receptors, regardless of N-glycosylation, thereby inhibiting neurotransmission and LTP in the dentate gyrus.
Maruo
Keishi
K
Department of Physiology, Hyogo College of Medicine, 1-1 Mukogawa-cho, Nishinomiya 663-8501, Japan.
Nagata
Tetsu
T
Yamamoto
Satoshi
S
Nagai
Kaoru
K
Yajima
Yukio
Y
Maruo
Soji
S
Nishizaki
Tomoyuki
T
D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D004347:Drug Interactions; D004558:Electric Stimulation; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology; D006031:Glycosylation / Q000187:drug effects; D006624:Hippocampus / Q000187:drug effects / Q000502:physiology; D066298:In Vitro Techniques; D007608:Kainic Acid / Q000494:pharmacology; D017774:Long-Term Potentiation / Q000187:drug effects; D008564:Membrane Potentials / Q000187:drug effects; D016202:N-Methylaspartate / Q000494:pharmacology; D009474:Neurons / Q000187:drug effects / Q000502:physiology; D018408:Patch-Clamp Techniques; D051381:Rats; D018091:Receptors, AMPA / Q000037:antagonists & inhibitors* / Q000502:physiology; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors* / Q000502:physiology; D013997:Time Factors; D014415:Tunicamycin / Q000494:pharmacology*
D000900:Anti-Bacterial Agents; D018690:Excitatory Amino Acid Agonists; D018091:Receptors, AMPA; D016194:Receptors, N-Methyl-D-Aspartate; D014415:Tunicamycin; D016202:N-Methylaspartate; D007608:Kainic Acid