The lateral pressure profile in membranes: a physical mechanism of general anesthesia

被引:58
作者
Cantor, RS [1 ]
机构
[1] Dartmouth Coll, Dept Chem, Hanover, NH 03755 USA
关键词
lipid-mediated mechanism; lateral pressure; alkanol cutoff; perfluorocarbons;
D O I
10.1016/S0378-4274(98)00220-3
中图分类号
R99 [毒物学(毒理学)];
学科分类号
100405 ;
摘要
1. A lipid-mediated mechanism of general anesthesia is suggested and investigated using lattice statistical thermodynamics. 2. Anesthetics are predicted to shift the distribution of lateral pressure within a lipid bilayer, and thus alter the mechanical work required to open ion channel proteins, if channel opening is accompanied by a non-uniform change in cross-sectional area of the protein. 3. Calculations based on this mechanical thermodynamic hypothesis yield qualitative agreement with anesthetic potency at clinical anesthetic membrane concentrations, and predict the alkanol cutoff and anomalously low potencies of strongly hydrophobic molecules with little attraction for the aqueous interface, such as perfluorocarbons. (C) 1998 Elsevier Science Ireland Ltd. All rights reserved.
引用
收藏
页码:451 / 458
页数:8
相关论文
共 28 条
[21]   NONANESTHETIC ALCOHOLS DISSOLVE IN SYNAPTIC-MEMBRANES WITHOUT PERTURBING THEIR LIPIDS [J].
MILLER, KW ;
FIRESTONE, LL ;
ALIFIMOFF, JK ;
STREICHER, P .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1989, 86 (03) :1084-1087
[22]   Contrasting membrane localization and behavior of halogenated cyclobutanes that follow or violate the Meyer-Overton hypothesis of general anesthetic potency [J].
North, C ;
Cafiso, DS .
BIOPHYSICAL JOURNAL, 1997, 72 (04) :1754-1761
[23]  
Pohorille A., 1997, PROG COLL POL SCI S, V103, P29
[24]  
Safran S.A., 2003, Statistical Thermodynamics of Surfaces, Interfaces, and Membranes
[25]   Different distribution of fluorinated anesthetics and nonanesthetics in model membrane: A F-19 NMR study [J].
Tang, P ;
Yan, B ;
Xu, Y .
BIOPHYSICAL JOURNAL, 1997, 72 (04) :1676-1682
[26]   ACETYLCHOLINE-RECEPTOR CHANNEL IMAGED IN THE OPEN STATE [J].
UNWIN, N .
NATURE, 1995, 373 (6509) :37-43
[27]   NICOTINIC ACETYLCHOLINE-RECEPTOR AT 9-ANGSTROM RESOLUTION [J].
UNWIN, N .
JOURNAL OF MOLECULAR BIOLOGY, 1993, 229 (04) :1101-1124
[28]   SURFACE-ORIENTED SATURABLE BINDING OF HALOTHANE WITH MICELLES - PARAMAGNETIC RELAXATION OF F-19 NMR SPIN-LATTICE RELAXATION RATE AND GAS-CHROMATOGRAPHY STUDIES [J].
YOSHINO, A ;
MURATE, K ;
YOSHIDA, T ;
OKABAYASHI, H ;
KRISHNA, PR ;
KAMAYA, H ;
UEDA, I .
JOURNAL OF COLLOID AND INTERFACE SCIENCE, 1994, 166 (02) :375-382