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Suppression of the induction of long‐term depression by carbon monoxide in rat cerebellar slices
Author(s) -
Shibuki Katsuei,
Kimura Shinji,
Wakatsuki Hidemitsu
Publication year - 2001
Publication title -
european journal of neuroscience
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.346
H-Index - 206
eISSN - 1460-9568
pISSN - 0953-816X
DOI - 10.1046/j.0953-816x.2000.01413.x
Subject(s) - cerebellum , chemistry , carbon monoxide , endogeny , glutamate receptor , intracellular , nitric oxide , long term depression , medicine , pharmacology , biophysics , endocrinology , biology , biochemistry , receptor , ampa receptor , catalysis
Carbon monoxide (CO) suppresses brain functions at doses lower than that suppressing oxygen (O 2 ) supply to the brain, and the cerebellum is one of the sites most susceptible to the neurotoxic effects of CO. We investigated the effects of CO on the induction of cerebellar long‐term depression (LTD) in the synapses between parallel fibres (PFs) and Purkinje cells. CO, at concentrations between 8 n m and 5 µ m , exhibited almost no effect on synaptic responses in Purkinje cells, O 2 consumption and NO release from PFs in rat cerebellar slices. However, the induction of LTD was significantly suppressed by CO at concentrations between 40 and 200 n m . The suppressive effect of 40 n m CO was antagonized by 10 µ m NOR3, an NO donor. In contrast, CO exhibited no clear effect on the induction of LTD at concentrations between 1 and 5 µ m . The induction of LTD, suppressed by 10 µ m N G ‐nitro‐ l ‐arginine, an inhibitor of NO synthase, was not restored by 5 µ m CO. CO is not only a neurotoxic substance but also a candidate for an intercellular messenger. δ‐Aminolevulinate (30 µ m ), a substance facilitating endogenous CO production, suppressed the induction of LTD, and the effect of δ‐aminolevulinate was antagonized by 10 µ m NOR3. These findings suggest that CO may have a suppressive effect on the induction of cerebellar LTD at nanomolar concentrations, probably via its effects on NO/cGMP signalling.