Nitric oxide inhibits depolarization-evoked glutamate release from rat cerebellar granule cells.
Nitric oxide (NO) modulates the release of various neurotransmitters, some of these are considered to be involved in neuronal plasticity that includes long-term depression in the cerebellum. To date, there have been no reports on the modulation of the exocytotic release of neurotransmitters in the cerebellar granule cells (CGCs) by NO. The aim of this study was to investigate the effects of NO on the exocytotic release of glutamate from rat CGCs. Treatment with NO-related reagents revealed that NO inhibited high-K(+)-evoked glutamate release. Clostridium botulinum type B neurotoxin (BoNT/B) attenuated the enhancement of glutamate release caused by NO synthase (NOS) inhibition; this indicates that NO acts on the high-K(+)-evoked exocytotic pathway. cGMP-related reagents did not affect the high-K(+)-evoked glutamate release. NO-related reagents did not affect Ca(2+) ionophore-induced glutamate release, suggesting that NO inhibits Ca(2+) entry through voltage-dependent Ca(2+) channels (VDCC). Monitoring of intracellular Ca(2+) revealed that NO inhibited high-K(+)-evoked Ca(2+) entry. L-type VDCC blockers inhibited glutamate release and NO did not have an additive effect on the inhibition produced by the L-type VDCC blocker. The inhibition of the high-K(+)-evoked glutamate release by NO was abolished by a reducing reagent; this suggested that NO regulates the high-K(+)-evoked glutamate release from CGCs by redox modulation.
Tsutsuki
Hiroyasu
H
Department of Biological Science, Graduate School of Science, Osaka Prefecture University, Gakuen-cho, Sakai, Osaka, Japan.
Kohda
Tomoko
T
Hara
Masayuki
M
Kozaki
Shunji
S
Ihara
Hideshi
H
D000818:Animals; D015153:Blotting, Western; D002531:Cerebellum / Q000166:cytology / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D003594:Cytoplasmic Granules / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D018698:Glutamic Acid / Q000378:metabolism*; D007150:Immunohistochemistry; D066298:In Vitro Techniques; D009569:Nitric Oxide / Q000494:pharmacology*; D052248:Nitric Oxide Synthase Type I / Q000378:metabolism; D011188:Potassium / Q000494:pharmacology; D051381:Rats
D009569:Nitric Oxide; D018698:Glutamic Acid; D052248:Nitric Oxide Synthase Type I; D011188:Potassium