Anesthetic effects on glutamate-stimulated increase in intraneuronal calcium.
The aim of these investigations was to examine directly with fura-2 microspectrofluorimetry, the effects of general anesthetics on the resting level and glutamate-stimulated increase of intraneuronal free calcium ([Ca++]i) in cultured hippocampal neurons. Media were chosen for the preferential activation by glutamate of either the quisqualate (QUIS media) or N-methyl-D-aspartate (NMDA media) receptor subtypes. Continuous perfusion (20 min) of either media that had been saturated with isoflurane (0.5-4%) or, in some cases halothane (3-4%), produced only small and inconsistent changes in resting [Ca++]i. The rise in [Ca++]i induced by glutamate (or in some cases, NMDA) that was applied in the mainstream of QUIS or NMDA media was attenuated greatly during such applications of isoflurane or halothane for 6 to 20 min. Analysis of concentration-response relationships revealed that the EC50 values for the isoflurane-depressions were 1.7% for the Ca response to glutamate in QUIS media and 1.2% in NMDA media. Application of isoflurane blunted the peak increases in [Ca++]i produced by brief (1 min) applications of 50 mM K. Verapamil (25 microM) did not reduce the resting [Ca++]i and had long-lasting depressant effects on glutamate-stimulated increases in [Ca++]i in NMDA media. The effects of 2% isoflurane and verapamil were approximately additive. These investigations provided evidence that isoflurane reduced the increase in [Ca++]i which resulted from Ca influx linked directly to receptors for glutamate in addition to Ca entry due to activation of voltage-gated Ca channels.
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Department of Pharmacology & Therapeutics, Faculty of Medicine, University of British Columbia, Vancouver, Canada.
el-Beheiry
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Baimbridge
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D000596:Amino Acids / Q000494:pharmacology; D000777:Anesthetics / Q000494:pharmacology*; D000818:Animals; D002118:Calcium / Q000032:analysis*; D002121:Calcium Channel Blockers / Q000494:pharmacology; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D016257:Fura-2; D005971:Glutamates / Q000494:pharmacology*; D006221:Halothane / Q000494:pharmacology; D006624:Hippocampus / Q000166:cytology / Q000378:metabolism; D007424:Intracellular Fluid / Q000378:metabolism; D007530:Isoflurane / Q000494:pharmacology; D016202:N-Methylaspartate / Q000494:pharmacology; D009474:Neurons / Q000737:chemistry* / Q000187:drug effects / Q000378:metabolism; D016318:Quisqualic Acid / Q000494:pharmacology; D051381:Rats; D013050:Spectrometry, Fluorescence; D014700:Verapamil / Q000494:pharmacology
D000596:Amino Acids; D000777:Anesthetics; D002121:Calcium Channel Blockers; D005971:Glutamates; D016202:N-Methylaspartate; D016318:Quisqualic Acid; D014700:Verapamil; D007530:Isoflurane; D002118:Calcium; D016257:Fura-2; D006221:Halothane