Anesthetic, effects membrane fluidity

The primary site of action is postulated to be the Hpid matrix of cell membranes. The Hpid properties which are said to be altered vary from theory to theory and include enhancing membrane fluidity volume expansion melting of gel phases increasing membrane thickness, surface tension, and lateral surface pressure and encouraging the formation of polar dislocations (10,11). Most theories postulate that changes in the Hpids influence the activities of cmcial membrane proteins such as ion channels. The Hpid theories suffer from an important drawback at clinically used concentrations, the effects of inhalational anesthetics on Hpid bilayers are very small and essentially undetectable (6,12,13). 

Although ethanol is amphipathic, it has substantial llpid solubility, and ethanol-induced Intoxication and its ultimate anesthetic effect are also likely due to increased fluidity of neuronal membranes, resulting In impairment of nerve conduction to the CNS. 

The answer is E. Anesthetics are highly lipid-soluble and experiments with isolated membranes indicate that these molecules can dissolve in the hydrophobic center of the membrane bilayer. This causes a measurable increase in the membrane fluidity by disrupting the packed structure of phospholipids tails. This is considered to be the main, direct mechanism by which this class of drugs inhibits neurotransmission (pain sensations) in neurons. Hallucinogens and opiates may also affect membrane fluidity, but their effects occur by indirect mechanisms, resulting from changes in the protein or lipid composition of the membranes. 

Despite more than 100 years of medical use, the mechanism of action of inhalation anesthetics is not well understood. Early theories of mechanism were based on the fact that anesthetic potency was highly correlated to an inhalation agent s lipid solubility. Consequently, it was believed that inhalation agents dissolved in the lipid bilayer of the cell membrane, increasing membrane fluidity and non-specifically disrupting the normal function of membrane proteins such as ion channels (Ueda Suzuki 1998). Increasing evidence now suggests that, rather than a non-specific cell membrane effect, there may in fact be relatively specific sites of action at cell and tissue level for... 

Local anesthetics. Anesthetics interact with membranes and increase the gel to liquid-crystalline transition of fully hydrated bilayers. They induce a volume expansion which has the opposite effect of HHP and so they antagonize the effect of HHP on membranes fluidity and volume, making membranes more fluid and expanded. The application of HHP to membrane-anesthetic systems may even result in the expulsion to the aqueous environment. The local anesthetic tetracaine (TTC) can be viewed as a model system for a large group of amphiphilic molecules. From volumetric measiuements on a sample containing e.g. 3 mol% TTC, it has been found that the main tansition at ambient pressure shifts to a lower temperature. The expansion coefficient a drastically increases relative to that of the pure lipid system in the gel phase, and the incorporation of the anesthetic into the DMPC bilayer causes an about 15 % decrease of relative to that of the pure lipid system. The addition of 3 mol% TTC shifts the pressure-induced liquid-crystalline to gel phase transition towards somewhat higher pressures. Larger values for the compressibilities are found for both lipid phases by addition of 3 mol% TTC, and there is no apparent difference in the coefficient of compressibility between the gel and liquid-crystalline phases. Comparison of the IR spectra of DMPC and DMPC/TTC mixtures at pH 5.5 as a function of pressure shows an abrupt... 

Like general anesthetics, ethanol appears to act by changing the fluidity of membrane lipids, leading to a perturbed function of the membrane proteins. During development of tolerance to ethanol, the membrane phospholipids acquire more saturated fatty acids, which seems to counteract the effects of ethanol on membrane function. 

Following Overton s early observation of the direct relationship between the efficacy of an alcohol and oil/water partition coefficient of that alcohol, most research concerning the mechanism of action of ethanol and similar anesthetics has focused on the interior of neuronal membranes and model membrane systems. The lipid perturbation hypothesis simply states that the effects of alcohols result from changes in the fluidity of the interior of the membrane. The observed changes in membrane order, however, are usually small or occur at nonphysiological concentrations of alcohol. ... 

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