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Membrane disordering by anesthetic drugs: relationship to synaptosomal sodium and calcium fluxes.
J Neurochem. 1985 Apr; 44(4):1274-81.JN

Abstract

The effects of membrane perturbants (ethanol, pentobarbital, chloroform, diethylether, phenytoin, cis-vaccenic acid methylester, and cis-vaccenoyl alcohol) on the lipid order of mouse brain synaptic plasma membranes (SPM) were tested by fluorescence polarization using 1,6-diphenyl-1,3,5-hexatriene (DPH) as a probe of the membrane core and 1-[4-(trimethylammonium)phenyl]-6-phenyl-1,3,5-hexatriene (TMA-DPH) as a probe of the membrane surface. The compounds decreased the fluorescence polarization of both probes, indicating that they disordered the membrane lipids. The decrease in polarization was, however, greater for DPH than for TMA-DPH, suggesting a greater effect on the membrane core than on the membrane surface. The voltage-dependent uptake of 24Na and 45Ca was studied in isolated mouse brain synaptosomes as a measure of membrane function. All of the compounds inhibited sodium influx, and their potencies for decreasing sodium uptake and fluorescence polarization of DPH were linearly correlated (r = 0.91). The relationship between changes in sodium influx and TMA-DPH polarization was less consistent (r = 0.66). Synaptosomal calcium uptake was inhibited by most, but not all, of the perturbants, but this inhibition was poorly correlated with changes in fluorescence polarization of DPH (r = 0.36) or TMA-DPH (r = 0.26). These results indicate that the function of synaptic sodium channels is correlated with lipid order in the hydrophobic core of the membrane and that the inhibitory effects of intoxicant-anesthetic drugs on neuronal sodium fluxes may be the result of their capacity to disorder these lipids. In contrast, the effects of drugs on voltage-dependent calcium channels were not clearly related to the capacity of these agents to disorder membrane lipids.

Authors

No affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, U.S. Gov't, Non-P.H.S.
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

2579208

Citation

Harris, R A., and P Bruno. "Membrane Disordering By Anesthetic Drugs: Relationship to Synaptosomal Sodium and Calcium Fluxes." Journal of Neurochemistry, vol. 44, no. 4, 1985, pp. 1274-81.
Harris RA, Bruno P. Membrane disordering by anesthetic drugs: relationship to synaptosomal sodium and calcium fluxes. J Neurochem. 1985;44(4):1274-81.
Harris, R. A., & Bruno, P. (1985). Membrane disordering by anesthetic drugs: relationship to synaptosomal sodium and calcium fluxes. Journal of Neurochemistry, 44(4), 1274-81.
Harris RA, Bruno P. Membrane Disordering By Anesthetic Drugs: Relationship to Synaptosomal Sodium and Calcium Fluxes. J Neurochem. 1985;44(4):1274-81. PubMed PMID: 2579208.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Membrane disordering by anesthetic drugs: relationship to synaptosomal sodium and calcium fluxes. AU - Harris,R A, AU - Bruno,P, PY - 1985/4/1/pubmed PY - 1985/4/1/medline PY - 1985/4/1/entrez SP - 1274 EP - 81 JF - Journal of neurochemistry JO - J Neurochem VL - 44 IS - 4 N2 - The effects of membrane perturbants (ethanol, pentobarbital, chloroform, diethylether, phenytoin, cis-vaccenic acid methylester, and cis-vaccenoyl alcohol) on the lipid order of mouse brain synaptic plasma membranes (SPM) were tested by fluorescence polarization using 1,6-diphenyl-1,3,5-hexatriene (DPH) as a probe of the membrane core and 1-[4-(trimethylammonium)phenyl]-6-phenyl-1,3,5-hexatriene (TMA-DPH) as a probe of the membrane surface. The compounds decreased the fluorescence polarization of both probes, indicating that they disordered the membrane lipids. The decrease in polarization was, however, greater for DPH than for TMA-DPH, suggesting a greater effect on the membrane core than on the membrane surface. The voltage-dependent uptake of 24Na and 45Ca was studied in isolated mouse brain synaptosomes as a measure of membrane function. All of the compounds inhibited sodium influx, and their potencies for decreasing sodium uptake and fluorescence polarization of DPH were linearly correlated (r = 0.91). The relationship between changes in sodium influx and TMA-DPH polarization was less consistent (r = 0.66). Synaptosomal calcium uptake was inhibited by most, but not all, of the perturbants, but this inhibition was poorly correlated with changes in fluorescence polarization of DPH (r = 0.36) or TMA-DPH (r = 0.26). These results indicate that the function of synaptic sodium channels is correlated with lipid order in the hydrophobic core of the membrane and that the inhibitory effects of intoxicant-anesthetic drugs on neuronal sodium fluxes may be the result of their capacity to disorder these lipids. In contrast, the effects of drugs on voltage-dependent calcium channels were not clearly related to the capacity of these agents to disorder membrane lipids. SN - 0022-3042 UR - https://www.unboundmedicine.com/medline/citation/2579208/Membrane_disordering_by_anesthetic_drugs:_relationship_to_synaptosomal_sodium_and_calcium_fluxes_ L2 - https://onlinelibrary.wiley.com/resolve/openurl?genre=article&sid=nlm:pubmed&issn=0022-3042&date=1985&volume=44&issue=4&spage=1274 DB - PRIME DP - Unbound Medicine ER -