Nitrous oxide directly inhibits action potential-dependent neurotransmission from single presynaptic boutons adhering to rat hippocampal CA3 neurons.
We evaluated the effects of N2O on synaptic transmission using a preparation of mechanically dissociated rat hippocampal CA3 neurons that allowed assays of single bouton responses evoked from native functional nerve endings. We studied the effects of N2O on GABAA, glutamate, AMPA and NMDA receptor-mediated currents (IGABA, IGlu, IAMPA and INMDA) elicited by exogenous application of GABA, glutamate, (S)-AMPA, and NMDA and spontaneous, miniature, and evoked GABAergic inhibitory and glutamatergic excitatory postsynaptic current (sIPSC, mIPSC, eIPSC, sEPSC, mEPSC and eEPSC) in mechanically dissociated CA3 neurons. eIPSC and eEPSC were evoked by focal electrical stimulation of a single bouton. Administration of 70% N2O altered neither IGABA nor the frequency and amplitude of both sIPSCs and mIPSCs. In contrast, N2O decreased the amplitude of eIPSCs, while increasing failure rates (Rf) and paired-pulse ratios (PPR) in a concentration-dependent manner. On the other hand, N2O decreased IGlu, IAMPA and INMDA. Again N2O did not change the frequency and amplitude of either sEPSCs of mEPSCs. N2O also decreased amplitudes of eEPSCs with increased Rf and PPR. The decay phases of all synaptic responses were unchanged. The present results indicated that N2O inhibits the activation of AMPA/KA and NMDA receptors and also that N2O preferentially depress the action potential-dependent GABA and glutamate releases but had little effects on spontaneous and miniature releases.
Research Division for Clinical Pharmacology, Medical Corporation, Jyuryo Group, Kumamoto Kinoh Hospital, 6-8-1 Yamamuro, Kitaku, Kumamoto 860-8518, Japan; Research Division for Life Science, Kumamoto Health Science University, 325 Izumi-machi, Kitaku, Kumamoto 861-5598, Japan.
Masahito
M
Wakita
Research Division of Neurophysiology, Kitamoto Hospital, 3-7-6 Kawarasone, Koshigaya, Saitama 343-0821, Japan.
Naoki
N
Kotani
Research Division for Life Science, Kumamoto Health Science University, 325 Izumi-machi, Kitaku, Kumamoto 861-5598, Japan.
Toshitaka
T
Yamaga
Research Division for Clinical Pharmacology, Medical Corporation, Jyuryo Group, Kumamoto Kinoh Hospital, 6-8-1 Yamamuro, Kitaku, Kumamoto 860-8518, Japan; Research Division for Life Science, Kumamoto Health Science University, 325 Izumi-machi, Kitaku, Kumamoto 861-5598, Japan; Research Division of Neurophysiology, Kitamoto Hospital, 3-7-6 Kawarasone, Koshigaya, Saitama 343-0821, Japan. Electronic address: akaike.n@juryo.or.jp.
Norio
N
Akaike
D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D056654:CA3 Region, Hippocampal / Q000187:drug effects*; D004558:Electric Stimulation; D005260:Female; D059330:GABAergic Neurons / Q000187:drug effects; D018698:Glutamic Acid / Q000494:pharmacology; D053444:Inhibitory Postsynaptic Potentials / Q000187:drug effects; D008297:Male; D016202:N-Methylaspartate / Q000494:pharmacology; D009609:Nitrous Oxide / Q000494:pharmacology*; D017729:Presynaptic Terminals / Q000187:drug effects*; D051381:Rats; D017208:Rats, Wistar; D009435:Synaptic Transmission / Q000187:drug effects; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid / Q000494:pharmacology; D005680:gamma-Aminobutyric Acid / Q000494:pharmacology
D018698:Glutamic Acid; D005680:gamma-Aminobutyric Acid; D016202:N-Methylaspartate; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid; D009609:Nitrous Oxide
Focal electrical stimulation; GABA; Glutamate; Nitrous oxide; Synaptic neurotransmission; “Synaptic-bouton” preparation