Biomaterial Database

Different effects of volatile anesthetics and polyhalogenated alkanes on depolarization-evoked glutamate release in rat cortical brain slices. 1999

H Eilers, and C H Kindler, and P E Bickler

Department of Anesthesia and Perioperative Care, University of California San Francisco, 94143-0648, USA. eilers@itsa.ucsf.edu

Anesthetics cause a reduction in excitatory neurotransmission that may be important in the mechanisms of in vivo anesthetic action. Because glutamate is the major excitatory neurotransmitter in mammalian brain, evaluation of anesthetic effects on induced glutamate release is relevant for studying this potential mechanism of anesthetic action. In the present study, we compared the effects of anesthetics and nonanesthetics (halogenated alkanes that disobey the Meyer-Overton hypothesis) on depolarization-evoked glutamate release. Glutamate released from rat cortical brain slices after chemically induced depolarization (50 mM KCl) was measured continuously using an enzymatic fluorescence assay. The effects of the volatile anesthetics isoflurane and enflurane were compared with the effects of the transitional compound 1,1,2-trichlorotrifluoroethane, the nonanesthetic compound 1,2-dichlorohexafluorocyclobutane, and other polyhalogenated alkanes. Tested concentrations included effective anesthetic concentrations for the anesthetics and transitional compounds, and concentrations predicted to be anesthetic based on lipid solubility for the nonanesthetics. Isoflurane dose-dependently reduced depolarization-evoked glutamate release in cortical brain slices. Isoflurane and enflurane at concentrations equivalent to 1 minimum alveolar anesthetic concentration (MAC) reduced the KCl-evoked release to 20% and 17% of control, respectively. The transitional compound 1,1,2-trichlorotrifluoroethane at 210 microM (approximately 1.2 MAC) reduced glutamate release to 47%, and the nonanesthetic 1,2-dichlorohexafluorocyclobutane increased glutamate release at 70 microM (approximately 3 MAC). These findings support the hypothesis that the modulation of excitatory neurotransmission might be responsible, in part, for in vivo anesthetic action. CONCLUSIONS The volatile anesthetics isoflurane and enflurane reduce depolarization-evoked glutamate release in rat brain slices. The transitional compound 1,1,2-trichlorotrifluoroethane reduces glutamate release to a much lesser extent, and the nonanesthetic 1,2-dichlorohexafluorocyclobutane does not reduce glutamate release. These findings support the hypothesis that the modulation of excitatory neurotransmission might be responsible, in part, for in vivo anesthetic action.

UI	MeSH Term	Description	Entries
D008564	Membrane Potentials	The voltage differences across a membrane. For cellular membranes they are computed by subtracting the voltage measured outside the membrane from the voltage measured inside the membrane. They result from differences of inside versus outside concentration of potassium, sodium, chloride, and other ions across cells' or ORGANELLES membranes. For excitable cells, the resting membrane potentials range between -30 and -100 millivolts. Physical, chemical, or electrical stimuli can make a membrane potential more negative (hyperpolarization), or less negative (depolarization).	Resting Potentials,Transmembrane Potentials,Delta Psi,Resting Membrane Potential,Transmembrane Electrical Potential Difference,Transmembrane Potential Difference,Difference, Transmembrane Potential,Differences, Transmembrane Potential,Membrane Potential,Membrane Potential, Resting,Membrane Potentials, Resting,Potential Difference, Transmembrane,Potential Differences, Transmembrane,Potential, Membrane,Potential, Resting,Potential, Transmembrane,Potentials, Membrane,Potentials, Resting,Potentials, Transmembrane,Resting Membrane Potentials,Resting Potential,Transmembrane Potential,Transmembrane Potential Differences
D011189	Potassium Chloride	A white crystal or crystalline powder used in BUFFERS; FERTILIZERS; and EXPLOSIVES. It can be used to replenish ELECTROLYTES and restore WATER-ELECTROLYTE BALANCE in treating HYPOKALEMIA.	Slow-K,Chloride, Potassium
D002540	Cerebral Cortex	The thin layer of GRAY MATTER on the surface of the CEREBRAL HEMISPHERES that develops from the TELENCEPHALON and folds into gyri and sulci. It reaches its highest development in humans and is responsible for intellectual faculties and higher mental functions.	Allocortex,Archipallium,Cortex Cerebri,Cortical Plate,Paleocortex,Periallocortex,Allocortices,Archipalliums,Cerebral Cortices,Cortex Cerebrus,Cortex, Cerebral,Cortical Plates,Paleocortices,Periallocortices,Plate, Cortical
D004305	Dose-Response Relationship, Drug	The relationship between the dose of an administered drug and the response of the organism to the drug.	Dose Response Relationship, Drug,Dose-Response Relationships, Drug,Drug Dose-Response Relationship,Drug Dose-Response Relationships,Relationship, Drug Dose-Response,Relationships, Drug Dose-Response
D000473	Alkanes	The generic name for the group of aliphatic hydrocarbons Cn-H2n+2. They are denoted by the suffix -ane. (Grant & Hackh's Chemical Dictionary, 5th ed)	Alkane
D000818	Animals	Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA.	Animal,Metazoa,Animalia
D017207	Rats, Sprague-Dawley	A strain of albino rat used widely for experimental purposes because of its calmness and ease of handling. It was developed by the Sprague-Dawley Animal Company.	Holtzman Rat,Rats, Holtzman,Sprague-Dawley Rat,Rats, Sprague Dawley,Holtzman Rats,Rat, Holtzman,Rat, Sprague-Dawley,Sprague Dawley Rat,Sprague Dawley Rats,Sprague-Dawley Rats
D051381	Rats	The common name for the genus Rattus.	Rattus,Rats, Laboratory,Rats, Norway,Rattus norvegicus,Laboratory Rat,Laboratory Rats,Norway Rat,Norway Rats,Rat,Rat, Laboratory,Rat, Norway,norvegicus, Rattus
D018685	Anesthetics, Inhalation	Gases or volatile liquids that vary in the rate at which they induce anesthesia; potency; the degree of circulation, respiratory, or neuromuscular depression they produce; and analgesic effects. Inhalation anesthetics have advantages over intravenous agents in that the depth of anesthesia can be changed rapidly by altering the inhaled concentration. Because of their rapid elimination, any postoperative respiratory depression is of relatively short duration. (From AMA Drug Evaluations Annual, 1994, p173)	Inhalation Anesthetic,Inhalation Anesthetics,Anesthetic Gases,Anesthetic, Inhalation,Gases, Anesthetic
D018698	Glutamic Acid	A non-essential amino acid naturally occurring in the L-form. Glutamic acid is the most common excitatory neurotransmitter in the CENTRAL NERVOUS SYSTEM.	Aluminum L-Glutamate,Glutamate,Potassium Glutamate,D-Glutamate,Glutamic Acid, (D)-Isomer,L-Glutamate,L-Glutamic Acid,Aluminum L Glutamate,D Glutamate,Glutamate, Potassium,L Glutamate,L Glutamic Acid,L-Glutamate, Aluminum