PMID- 9756375
OWN - NLM
STAT- MEDLINE
DCOM- 19981223
LR  - 20141120
IS  - 0007-1188 (Print)
IS  - 0007-1188 (Linking)
VI  - 124
IP  - 8
DP  - 1998 Aug
TI  - Presynaptic and postsynaptic actions of halothane at glutamatergic synapses in 
      the mouse hippocampus.
PG  - 1607-14
AB  - Whole-cell patch-clamp recordings in adult mouse hippocampal slices were used to 
      test the mechanism by which the volatile anesthetic halothane inhibits glutamate 
      receptor-mediated synaptic transmission. Non-N-methyl-D-aspartate (nonNMDA) and 
      NMDA receptor-mediated currents in CA1 pyramidal cells were pharmacologically 
      isolated by bath application of D,L-2-amino-5-phosphonovaleric acid (APV; 100 
      microM) or 6-cyano-7-nitro-quinoxaline-2,3-dione (CNQX; 5 microM), respectively. 
      Halothane blocked both nonNMDA and NMDA receptor-mediated excitatory postsynaptic 
      currents (EPSCs) to a similar extent (IC50 values of 0.66 and 0.57 mM, 
      respectively). Partial blockade of the EPSCs by lowering the extracellular 
      concentration of calcium ([Ca2+]o), but not by application of CNQX (1 microM), 
      was accompanied by an increase in paired-pulse facilitation (PPF). 
      Halothane-induced blockade of the EPSCs also was associated with an increase in 
      PPF. The effects of halothane on 
      alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) and NMDA 
      receptor-mediated currents induced by agonist iontophoresis, were compared. 
      AMPA-induced currents were blocked with an IC50 of 1.7 mM. NMDA-induced currents 
      were significantly less sensitive to halothane (IC50 of 5.9 mM). The effect of 
      halothane on iontophoretic AMPA dose-response curves was tested. Halothane 
      suppressed the maximal response to AMPA without affecting its EC50, suggesting a 
      noncompetitive mechanism of inhibition. All effects of halothane were reversible 
      upon termination of the exposure to the drug. These data suggest that halothane 
      blocks central glutamatergic synaptic transmission by presynaptically inhibiting 
      glutamate release and postsynaptically blocking the AMPA subtype of glutamate 
      receptors.
FAU - Kirson, E D
AU  - Kirson ED
AD  - Department of Physiology, Hebrew University-Hadassah School of Medicine, 
      Jerusalem, Israel.
FAU - Yaari, Y
AU  - Yaari Y
FAU - Perouansky, M
AU  - Perouansky M
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Br J Pharmacol
JT  - British journal of pharmacology
JID - 7502536
RN  - 0 (Anesthetics, Inhalation)
RN  - 0 (Excitatory Amino Acid Antagonists)
RN  - 0 (Receptors, AMPA)
RN  - 0 (Receptors, N-Methyl-D-Aspartate)
RN  - 0 (Receptors, Presynaptic)
RN  - 3KX376GY7L (Glutamic Acid)
RN  - UQT9G45D1P (Halothane)
SB  - IM
MH  - Anesthetics, Inhalation/*pharmacology
MH  - Animals
MH  - Excitatory Amino Acid Antagonists/*pharmacology
MH  - Glutamic Acid/*physiology
MH  - Halothane/*pharmacology
MH  - Hippocampus/drug effects/*metabolism
MH  - In Vitro Techniques
MH  - Iontophoresis
MH  - Membrane Potentials/drug effects
MH  - Mice
MH  - Patch-Clamp Techniques
MH  - Receptors, AMPA/antagonists & inhibitors
MH  - Receptors, N-Methyl-D-Aspartate/antagonists & inhibitors
MH  - Receptors, Presynaptic/*drug effects
MH  - Synapses/*drug effects
PMC - PMC1565559
EDAT- 1998/10/02 00:00
MHDA- 1998/10/02 00:01
PMCR- 1999/08/01
CRDT- 1998/10/02 00:00
PHST- 1998/10/02 00:00 [pubmed]
PHST- 1998/10/02 00:01 [medline]
PHST- 1998/10/02 00:00 [entrez]
PHST- 1999/08/01 00:00 [pmc-release]
AID - 0701996 [pii]
AID - 10.1038/sj.bjp.0701996 [doi]
PST - ppublish
SO  - Br J Pharmacol. 1998 Aug;124(8):1607-14. doi: 10.1038/sj.bjp.0701996.