| Carbon dioxide negatively modulates N-methyl-D-aspartate receptors. | |
| | |
MedLine Citation:
|
PMID: 18791188 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
|
BACKGROUND: Carbon dioxide (CO2) dose-dependently decreases minimum alveolar concentration (MAC) of anaesthetics in rats. CO2 also dose-dependently decreases cerebrospinal fluid pH. N-methyl-D-aspartate (NMDA) channels exhibit pH sensitivity and are putative targets for inhaled anaesthetics. We hypothesized that CO2 dose-dependently decreases rat NMDA channel current via an acidifying effect at concentrations relevant to CO2 MAC. METHODS: To test this hypothesis, we studied rat NR1/NR2A glutamate receptors expressed in voltage-clamped Xenopus oocytes. To measure pH effects, we used perfusates adjusted between 7.3 and 5.3 with HCl. To measure CO2 effects, we used equimolar sodium perfusates containing either 0 or 24 mM NaHCO3 and CO2 between 0% and 87% atm. Solution compositions were measured using a blood gas analyser with values corrected using a calibrated pH meter and gas chromatograph with solutions at 37 degrees C. RESULTS: We found that decreasing pH decreased NMDA current. Moreover, pH effects produced by adding CO2 to NaHCO3-containing perfusates were identical to those produced by adding HCl to normal perfusates. The pH inhibiting 50% of NMDA current was 6.52. The CO2 concentration inhibiting 50% of rat NMDA current was 63% for solutions with 24 mM NaHCO3. CO2 exhibited a linear dose-dependent NMDA response analogous to that observed for in vivo CO2 anaesthetic potency in rats. CONCLUSIONS: CO2 and hydrogen ions act via the same mechanism to inhibit NMDA receptors. Moreover, CO2 inhibits rat NMDA receptors in a manner that is consistent with CO2 MAC-sparing effects in rats. |
| | |
Authors:
|
R J Brosnan; T L Pham |
Related Documents
:
|
11055748 - In vivo evaluation of hippocampal anti-oxidant ability of zonisamide in rats. 9550308 - Effect of nicotine or cotinine on metabolism of 4-methylnitrosamino-1-(3-pyridyl)-1-but... 8241708 - The function of coenzyme q in mitochondria. 1278118 - A fast in vitro effect of glucocorticoids on hepatic lipolysis. 2959918 - Metabolism in rats of p-cymene derivatives: carvacrol and thymol. 3392658 - Complexing activity of 2,3-dimercapto-1-propanesulfonate and its disulfide auto-oxidati... |
Publication Detail:
|
Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2008-09-12 |
Journal Detail:
|
Title: British journal of anaesthesia Volume: 101 ISSN: 1471-6771 ISO Abbreviation: Br J Anaesth Publication Date: 2008 Nov |
Date Detail:
|
Created Date: 2008-10-15 Completed Date: 2008-11-18 Revised Date: - |
Medline Journal Info:
|
Nlm Unique ID: 0372541 Medline TA: Br J Anaesth Country: England |
Other Details:
|
Languages: eng Pagination: 673-9 Citation Subset: IM |
Affiliation:
|
Department of Surgical and Radiological Sciences, School of Veterinary Medicine, University of California, Davis, CA 95616, USA. rjbrosnan@ucdavis.edu |
Export Citation:
|
APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
|
Animals Carbon Dioxide / pharmacology* Cells, Cultured Dose-Response Relationship, Drug Female Hydrogen-Ion Concentration Oocytes / metabolism Patch-Clamp Techniques Receptors, N-Methyl-D-Aspartate / antagonists & inhibitors*, metabolism Xenopus laevis |
| Chemical | |
Reg. No./Substance:
|
0/Receptors, N-Methyl-D-Aspartate; 124-38-9/Carbon Dioxide |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
Previous Document: Hyperventilation-induced hypocapnia changes the pattern of electroencephalographic bicoherence growt...
Next Document: Effects of clonidine on lidocaine-induced inhibition of axonal transport in cultured mouse dorsal ro...