THE PERMEABILITY OF MEMBRANES 139 



For example, capryl alcohol is a powerful anaesthetic, its " critical concentration " (Overton) 

 being 0'0004 molar, compared with ethyl alcohol at O3 molar, that is, it is 750 times as powerful 

 as ethyl alcohol. But benzene is a very poor anaesthetic, although its lipoid solubility is as 

 great as that of capryl alcohol. The fact that benzene is only slightly soluble in water does not 

 account for the fact, since, according to Rothmund (1907, p. 75), it is soluble in water to the 

 extent of 1 '4 parts in 2,000, while capryl alcohol is only soluble to the extent of 1 part in 2,000. 



If lipoid solubility were the only condition making a particular substance 

 a narcotic, it would be expected that the greater the lipoid content of 'an organ, 

 the less would be the concentration of a certain narcotic required to produce its 

 effect. Although this applies when we compare the central nervous system with 

 other tissues, it has been shown by Choquard (1913) that it does not hold in the 

 case of the heart muscle and skeletal muscle. The former, according to Erlandsen 

 (1907), is considerably richer in lipoids than the latter and should therefore be 

 more sensitive to all lipoid-soluble narcotics. Choquard's experiments show 

 numerous exceptions. 



We turn now to experiments with regard to the effect of anaesthetics on 

 permeability. According to Lillie (1911), there is a general parallelism between 

 the effect of agents in producing a state of excitation and their power of 

 increasing the permeability of the cell membrane. If this is so, we should expect 

 the opposite effect on the membrane to be produced by narcotics, which abolish 

 the excitability. Lillie himself (1912, 2) has shown that the action of sodium 

 chloride in causing excitation in the Arenicola larva, along with escape of pigment, 

 is prevented by ether, alcohol, chloroform, and chloretone. He draws the con- 

 clusion that the characteristic effect of these substances is produced by an 

 action on the cell membrane, making it more resistant to the action of substances 

 which tend to increase its permeability. Although lipoid-soluble anaesthetics 

 enter the cell immediately, the fact that magnesium chloride is a powerful 

 anaesthetic, although it enters the cell with extreme slowness, indicates that 

 the effect is essentially on the boundary membrane itself. Further evidence of 

 the same nature is given in the experiments of Osterhout (1913) on Laminaria. 

 In ether of 1 per cent., the electrical resistance of the cells rises, showing a decrease 

 of permeability to salts, in 3 per cent., after a preliminary rise, the resistance 

 falls and the tissue is killed. After exposure to 1 per cent, ether, recovery is 

 complete ; since recovery is a distinctive mark of anaesthetic action proper, it 

 is reasonable to hold that it is the diminution of permeability which is associated 

 with this effect. 



As to the way in which the state of the lipoid constituents of the membrane is modified, 

 we are as yet in the dark. A purely solvent action is precluded, since the lipoids would be 

 washed away and the state be irreversible. This has been pointed out by Overton (1901, 

 p. 51). There is no evidence that the state of colloidal dispersion of the lipoid is altered, 

 that is as regards the number of particles. Lillie holds (1912, 1, p. 395) that the lipoid 

 particles must increase in size by taking up the anaesthetic. In fact, Calugareanu (1910, 

 p. 100) has seen this to occur in lecithin suspensions when ether or chloroform is added. 

 It is evident that such a process would tend to decrease the interstices or pores of the 

 membrane, if such a sieve-like structure be accepted, and that it would be reversible. 

 According to Loewe (1913), narcotics change lipoids from lyophile into lyophobe colloids by 

 surrounding them with an impermeable layer. Hence, such agents would diminish perme- 

 ability so far as the water in the colloidal particles acted as a solvent, or carrier for solutes. 

 No excitation would be possible in this state, because the membrane cannot be made 

 permeable. It is found, in fact, experimentally, that narcotics lower permeability. Are the 

 lipoid particles robbed of their water or not? The decrease of permeability indicates the 

 latter, for otherwise they would shrink and allow more watery space for diffusion. On 

 the other hand, the irreversible increase of permeability, leading to death, may well be due 

 to actual dissolving away of the lipoids. The investigations of Czapek (1911) have shown 

 that there is a close parallelism between the power of the various alcohols in killing cells and 

 their power of lowering surface tension. As already mentioned (page 52), when the surface 

 tension at the cell membrane is lowered to a certain degree, death results. This phenomenon 

 is undoubtedly connected with the various degrees of lipoid solubility shown by the series 

 of alcohols. It is difficult to say whether the surface tension as such plays any important 

 pa,rt. 



There is no doubt that adsorption of active substances, including narcotics, by 

 the constituents of the cell membrane must play a considerable part, and indeed 

 Straub (1912, p. 11) regards the adsorption theory as the most satisfactory one 

 in respect to alkaloids. 



