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PMID: 9786963 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

cAMP-dependent long-term potentiation of nitric oxide release from cerebellar parallel fibers in rats.

Kimura S, Uchiyama S, Takahashi HE, Shibuki K

Abstract

Nitric Oxide (NO) is released from parallel fibers (PFs) after PF stimulation. NO-cGMP signaling is essential for long-term depression (LTD) in cerebellar PF-Purkinje cell synapses, which also exhibit presynaptic long-term potentiation (LTP) after tetanic PF stimulation. This LTP is dependent on cAMP but not NO-cGMP signaling. In this study, we analyzed long-term changes of NO release from PFs in rat cerebellar slices using electrochemical NO probes. Repetitive PF stimulation at 10 Hz for 2 sec elicited a transient increase in NO concentration (2.2 +/- 0.1 nM; mean +/- SEM; n = 116). This NO release exhibited long-term potentiation (LTPNO) by 36 +/- 3% (n = 15) after tetanic PF stimulation. Induction of LTPNO was not affected by Glu receptor antagonists. NO release from PFs was also potentiated by L-Arg (ARG) (100 microM), forskolin (50 microM), and 8-bromo-cAMP (Br-cAMP) (1 mM) but not by 1,9-dideoxyforskolin (50 microM), a biologically inactive analog of forskolin. The potentiation induced by forskolin was significantly suppressed by H89 (10 microM), a blocker of cAMP-dependent protein kinase. The potentiation induced by forskolin, but not that induced by Arg, interfered with LTPNO. H89 (10 microM) and KT5720 (1 microM), another blocker of cAMP-dependent protein kinase, but not KT5823 (300 nM), a blocker of cGMP-dependent protein kinase, significantly suppressed LTPNO. These data indicate that neural NO release is under activity-dependent control, just as synaptic transmitter release is. LTPNO might play a role in cross talk between presynaptic and postsynaptic plasticity by facilitating NO-cGMP-dependent postsynaptic LTD after induction of cAMP-dependent presynaptic LTP and LTPNO.

MeSH Terms
8-Bromo Cyclic Adenosine Monophosphate/pharmacology Animals Arginine/pharmacology Cerebellum/metabolism Colforsin/analogs & derivatives,pharmacology Cyclic AMP/physiology Cyclic AMP-Dependent Protein Kinases/antagonists & inhibitors Enzyme Inhibitors/pharmacology Female In Vitro Techniques Isoquinolines/pharmacology Long-Term Potentiation/drug effects Male Nitric Oxide/metabolism Rats Rats, Wistar Sulfonamides
Chemicals
Enzyme Inhibitors Isoquinolines Sulfonamides Colforsin 8-Bromo Cyclic Adenosine Monophosphate Nitric Oxide Arginine Cyclic AMP Cyclic AMP-Dependent Protein Kinases N-(2-(4-bromocinnamylamino)ethyl)-5-isoquinolinesulfonamide
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Kimura S
Department of Neurophysiology, Brain Research Institute, School of Medicine, Niigata University, Niigata 951-8585, Japan.
Uchiyama S
Takahashi H E
Shibuki K
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Article Info
Journal
The Journal of neuroscience : the official journal of the Society for Neuroscience
Abbr.
J Neurosci
ISSN
0270-6474
Published
1998-11-01
Pages
8551-8
Language
English
Region
United States
NLM ID
8102140
PMCID
PMC6793512
Subset
IM
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