TY - JOUR
T1 - Blockers of adenosine A1, but not muscarinic acetylcholine, receptors improve excessive extracellular glutamate-induced synaptic depression
AU - Narimatsu, Eichi
AU - Niiya, Tomohisa
AU - Takada, Yukimasa
AU - Takahashi, Kazunobu
AU - Yamauchi, Masanori
AU - Yamakage, Michiaki
N1 - Funding Information:
This work was supported by a Grant-in-Aid for Scientific Research (C) ( 23592675 ) from the Japan Society for the Promotion of Science and by a departmental fund of Sapporo Medical University School of Medicine .
PY - 2013/2
Y1 - 2013/2
N2 - We investigated adenosinergic and cholinergic effects on excessive glutamate-induced depressions of central excitatory synaptic transmissions in vitro. From the CA1 region in rat hippocampal slices, orthodromically elicited population spikes (PSs) and field excitatory postsynaptic potentials (fEPSPs) at 0.1. Hz were simultaneously recorded. ANOVA was used for statistics, and p<0.05 was accepted as significant. Glutamate (10. mM for 10. min) completely depressed PSs and fEPSPs, which were partially recovered by the following washout for 40. min (67.5±15.7% and 65.4 ± 13.9% of the control, respectively, p<0.01, n=12). The recoveries in PSs and fEPSPs were exacerbated by edrophonium and carbamoylcholine but improved by non- and A1-selective adenosine receptor antagonists (p<0.01, n=6). The recovery in PSs, not that in fEPSPs, was exacerbated by adenosine, adenosine A1-receptor agonist and A2a-receptor antagonist (p<0.01, n=6). The effects of edrophonium were blocked by non-, M2- and M4-selective muscarinic acetylcholine receptor antagonists (p<0.01, n=6). Excessive glutamate depresses glutamatergic excitatory synaptic transmissions, which are exacerbated by muscarinic acetylcholine receptor stimulation but improved by adenosine A1 receptor block. Somatic excitability is impaired by excessive glutamate with adenosine A1 receptor stimulation.
AB - We investigated adenosinergic and cholinergic effects on excessive glutamate-induced depressions of central excitatory synaptic transmissions in vitro. From the CA1 region in rat hippocampal slices, orthodromically elicited population spikes (PSs) and field excitatory postsynaptic potentials (fEPSPs) at 0.1. Hz were simultaneously recorded. ANOVA was used for statistics, and p<0.05 was accepted as significant. Glutamate (10. mM for 10. min) completely depressed PSs and fEPSPs, which were partially recovered by the following washout for 40. min (67.5±15.7% and 65.4 ± 13.9% of the control, respectively, p<0.01, n=12). The recoveries in PSs and fEPSPs were exacerbated by edrophonium and carbamoylcholine but improved by non- and A1-selective adenosine receptor antagonists (p<0.01, n=6). The recovery in PSs, not that in fEPSPs, was exacerbated by adenosine, adenosine A1-receptor agonist and A2a-receptor antagonist (p<0.01, n=6). The effects of edrophonium were blocked by non-, M2- and M4-selective muscarinic acetylcholine receptor antagonists (p<0.01, n=6). Excessive glutamate depresses glutamatergic excitatory synaptic transmissions, which are exacerbated by muscarinic acetylcholine receptor stimulation but improved by adenosine A1 receptor block. Somatic excitability is impaired by excessive glutamate with adenosine A1 receptor stimulation.
KW - Acetylcholine
KW - Adenosine
KW - Atropine
KW - Hippocampus
KW - Somatic excitability
KW - Synaptic transmission
KW - Theophylline
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U2 - 10.1016/j.neures.2012.11.002
DO - 10.1016/j.neures.2012.11.002
M3 - Article
C2 - 23174314
AN - SCOPUS:84875377301
VL - 75
SP - 103
EP - 111
JO - Neuroscience Research
JF - Neuroscience Research
SN - 0168-0102
IS - 2
ER -