Document Detail


Presynaptic actions of general anesthetics are responsible for frequency-dependent modification of synaptic transmission in the rat hippocampal CA1.
MedLine Citation:
PMID:  20435940     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
BACKGROUND: In clinical anesthesia, robust surgical stress occasionally causes unintended light anesthesia during operation. To test the hypothesis that neural input condition could modify actions of general anesthetics as a result of presynaptic alteration in the central nervous system, we investigated the mechanisms by which the stimulus frequency modifies synaptic transmission of the rat hippocampus in the presence of general anesthetics. METHODS: Field population spikes (PSs) of CA1 pyramidal neurons were elicited using orthodromic stimulation of Schaffer collateral-commissural fibers (test-pulse). A second stimulating electrode was placed in the region of the alveus hippocampi to activate recurrent inhibition of area CA1 (pre-pulse). The pre-pulses were applied as train stimuli (100-200 Hz) to activate release and then deplete the neurotransmitter (gamma-aminobutyric acid [GABA]) at presynaptic terminals of inhibitory interneurons. RESULTS: After the activation of inhibitory interneurons with pre-pulses, both IV (thiopental and pentobarbital) and volatile (sevoflurane and isoflurane) anesthetics attenuated the PS amplitudes elicited with test-pulses (test-PS). The IV anesthetics, but not the volatile drugs, produced stimulus frequency- and use-dependent recurrent inhibition of test-PSs. Neither a GABA type A agonist nor a GABA uptake inhibitor produced frequency-dependent modification. The pre-pulse train protocol revealed that IV anesthetics, but not volatile drugs, can enhance GABA release from presynaptic terminals. CONCLUSIONS: IV anesthetics, but not volatile drugs, enhance the discharge of a readily releasable pool of GABA vesicles from presynaptic terminals. Depletion of an active pool of GABA after high-frequency stimuli would produce frequency- and use-dependent recurrent inhibition in the presence of IV anesthetics. The stimulus frequency-dependent modification of synaptic transmission might be responsible for the unsuccessful immobilization or hypnosis during general anesthesia after IV anesthetic administration.
Authors:
Koki Hirota; Rika Sasaki; Sheldon H Roth; Mitsuaki Yamazaki
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2010-04-30
Journal Detail:
Title:  Anesthesia and analgesia     Volume:  110     ISSN:  1526-7598     ISO Abbreviation:  Anesth. Analg.     Publication Date:  2010 Jun 
Date Detail:
Created Date:  2010-05-26     Completed Date:  2010-06-15     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  1310650     Medline TA:  Anesth Analg     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1607-13     Citation Subset:  AIM; IM    
Affiliation:
Department of Anesthesiology, Graduate School of Medicine and Pharmaceutical Science for Research, University of Toyama, 2633 Sugitani, Toyama 930-0194, Japan. koki@med.u-toyama.ac.j
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MeSH Terms
Descriptor/Qualifier:
Anesthetics, General / pharmacology*
Animals
Axons / physiology
CA1 Region, Hippocampal / anatomy & histology,  drug effects*,  physiology
Central Nervous System / drug effects
Dose-Response Relationship, Drug
Electric Stimulation
Electrophysiology
Isoflurane / pharmacology
Male
Methyl Ethers / pharmacology
Neurotransmitter Agents / metabolism
Neurotransmitter Uptake Inhibitors / pharmacology
Pyramidal Cells / physiology
Rats
Rats, Wistar
Receptors, GABA-A / agonists
Receptors, Presynaptic / drug effects*,  metabolism
Synaptic Transmission / drug effects*
Thiopental / pharmacology
gamma-Aminobutyric Acid / metabolism
Chemical
Reg. No./Substance:
0/Anesthetics, General; 0/Methyl Ethers; 0/Neurotransmitter Agents; 0/Neurotransmitter Uptake Inhibitors; 0/Receptors, GABA-A; 0/Receptors, Presynaptic; 26675-46-7/Isoflurane; 28523-86-6/sevoflurane; 56-12-2/gamma-Aminobutyric Acid; 76-75-5/Thiopental

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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