Abstract
The effects of three volatile anesthetics (isoflurane, enflurane, and halothane) on basal release of glutamate and GABA from isolated rat cerebrocortical nerve terminals (synaptosomes) were compared using a dual isotope superfusion method. Concentration-dependent effects on basal release differed between anesthetics and transmitters. Over a range of clinical concentrations (0.5–2× minimum alveolar concentration), basal glutamate release was inhibited by all three anesthetics, whereas basal GABA release was enhanced (isoflurane) or unaffected (enflurane and halothane). These effects may represent a balance of stimulatory and inhibitory mechanisms between transmitters and anesthetics. There were no significant differences between anesthetic effects on basal release in the absence or presence of external Ca2+, whereas intracellular Ca2+ buffering limited volatile anesthetic inhibition of basal glutamate release. Although these results demonstrate fundamental differences in anesthetic effects on basal release between glutamatergic and GABAergic nerve terminals, all three volatile anesthetics at clinical concentrations consistently reduced the ratio of basal glutamate to GABA release. These actions may contribute to the net depression of glutamatergic excitation and potentiation of GABAergic inhibition characteristic of general anesthesia.
Footnotes
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This work was supported by National Institutes of Health Grant GM 58055 and by the Department of Anesthesiology, Weill Medical College, Cornell University.
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doi:10.1124/jpet.105.090647.
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ABBREVIATIONS: CNS, central nervous system; BAPTA-AM, 1,2-bis(2-aminophenoxy)ethane-N,N,N′,N′-tetraacetic acid tetrakis(acetoxymethyl) ester; 4AP, 4-aminopyridine; MAC, minimum alveolar concentration; KHB, Krebs-HEPES buffer; mEPSCs, miniature excitatory postsynaptic currents; mIPSCs, miniature inhibitory postsynaptic currents; LDH, lactate dehydrogenase; FR, fractional release.
- Received June 7, 2005.
- Accepted September 15, 2005.
- The American Society for Pharmacology and Experimental Therapeutics
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