Abstract
A reversible nerve-blocking spin label, 2,2,6,6-tetramethylpiperidine-1-oxyl (TEMPO) was used to study the nature of anesthetic-binding sites in nerve membranes as a function of pressure. The nerve-blocking effect of TEMPO is enhanced under pressure. At atmospheric pressure, TEMPO blocks nerve conduction by solubilizing in the apolar region of the nerve membrane. However, the nerve-conduction-block by TEMPO at 150 atm of helium was related to the binding of TEMPO to a pressure-induced high-affinity polar site in the nerve membrane. The new TEMPO-binding site could not be detected in lipid model membranes and, thus, the involvement of membrane protein in the new site was inferred. Pressure may induce a nerve membrane conformation change in the presence of TEMPO.
The observation that under different pressure, a single anesthetic, i.e., TEMPO, was capable of blocking nerve conduction by binding to two different sites within the nerve membrane, supports the view that there are multiple anesthetic receptor sites, which differ in chemical composition and location within the nerve membrane. These sites, when occupied by different classes of anesthetics, produce the general phenomenon of nerve-conduction block. The enhancement of nerve-conduction block by pressure may be due to the increased concentration of TEMPO in the new site in the nerve membrane under pressure.
Keywords: anesthetics, anesthesia, conformation change, receptor, synaptosomes
Full text
PDF
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Hsia J. C., Chen W. L., Long R. A., Wong L. T., Kalow W. Existence of phospholipid bilayer structure in the inner membrane of mitochondria. Proc Natl Acad Sci U S A. 1972 Nov;69(11):3412–3415. doi: 10.1073/pnas.69.11.3412. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Hubbell W. L., McConnell H. M. Spin-label studies of the excitable membranes of nerve and muscle. Proc Natl Acad Sci U S A. 1968 Sep;61(1):12–16. doi: 10.1073/pnas.61.1.12. [DOI] [PMC free article] [PubMed] [Google Scholar]
- JOHNSON F. H., FLAGLER E. A. Hydrostatic pressure reversal of narcosis in tadpoles. Science. 1950 Jul 21;112(2899):91–92. doi: 10.1126/science.112.2899.91-a. [DOI] [PubMed] [Google Scholar]
- Johnson S. M., Bangham A. D. The action of anaesthetics on phospholipid membranes. Biochim Biophys Acta. 1969 Oct 14;193(1):92–104. doi: 10.1016/0005-2736(69)90062-5. [DOI] [PubMed] [Google Scholar]
- Johnson S. M., Miller K. W. Antagonism of pressure and anaesthesia. Nature. 1970 Oct 3;228(5266):75–76. doi: 10.1038/228075b0. [DOI] [PubMed] [Google Scholar]
- Johnson S. M., Miller K. W., Bangham A. D. The opposing effects of pressure and general anaesthetics on the cation permeability of liposomes of varying lipid composition. Biochim Biophys Acta. 1973 Apr 25;307(1):42–57. doi: 10.1016/0005-2736(73)90023-0. [DOI] [PubMed] [Google Scholar]
- Lever M. J., Miller K. W., Paton W. D., Smith E. B. Pressure reversal of anaesthesia. Nature. 1971 Jun 11;231(5302):368–371. doi: 10.1038/231368a0. [DOI] [PubMed] [Google Scholar]
- Metcalfe J. C., Seeman P., Burgen A. S. The proton relaxation of benzyl alcohol in erythrocyte membranes. Mol Pharmacol. 1968 Jan;4(1):87–95. [PubMed] [Google Scholar]
- Seeman P. The membrane actions of anesthetics and tranquilizers. Pharmacol Rev. 1972 Dec;24(4):583–655. [PubMed] [Google Scholar]
- Trudell J. R., Hubbell W. L., Cohen E. N., Kendig J. J. Pressure reversal of anesthesia: the extent of small-molecule exclusion from spin-labeled phospholipid model membranes. Anesthesiology. 1973 Mar;38(3):207–211. doi: 10.1097/00000542-197303000-00002. [DOI] [PubMed] [Google Scholar]
- Youngson A. F., Macdonald A. G. Interaction between halothane and hydrostatic pressure. Br J Anaesth. 1970 Sep;42(9):801–802. [PubMed] [Google Scholar]