Abstract
IT is generally accepted that neutral anaesthetics, such as the n-alkanols and n-alkanes, act from a hydrophobic site1. Discussion has tended to focus on the nature of this site and, particularly, whether it is located in a membrane protein or in the interior of a bilayer2,3. If the site is in a bilayer then the question arises as to how the proteins involved in nervous impulse propagation are affected. We present here new evidence concerning the anaesthetic properties of the n-alkanes which points to the bilayer as the site of action and also suggests a mechanism for the inhibition of impulse propagation. Briefly, the cut-off in anaesthetic potency on ascending the homologous series is found to be closely related to the decrease in adsorption of the alkane into a cholesterol-containing bilayer. In addition, the anaesthetic hydrocarbons produce a concentration-dependent increase in bilayer thickness. On the basis of these two observations, and from our knowledge of the properties of the ion channel-forming polypeptide gramicidin A (ref. 4) we propose that a thickening of the bilayer regions of the nerve membrane by the alkanes destabilises the open ionic channels formed during electrical excitation.
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HAYDON, D., HENDRY, B., LEVINSON, S. et al. The molecular mechanisms of anaesthesia. Nature 268, 356–358 (1977). https://doi.org/10.1038/268356a0
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DOI: https://doi.org/10.1038/268356a0
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