THE PERMEABILITY OF MEMBRANES 121 



I have shown experimentally to be the case, while Donnan (1911) has deduced it from 

 thermodynamic considerations. 



We see, therefore, that the presence of a colloidal salt within a membrane, 

 semi-permeable only as regards colloids, will not account for the unequal ratio of 

 potassium to sodium in the plasma and corpuscles of the rabbit. 



Consider next the case of the muscle cell. The experiments of Katz (1896, 

 p. 42) have shown that, in the rabbit, the ratio of the sodium to the potassium in 

 these cells is as 0'46 to 4 ; whereas, as we have seen, the corresponding numbers 

 for the blood plasma are as 4-44 to 0*259, and Fahr (1909) has made it practically 

 certain that the sodium of frog's muscle is contained only in the intercellular 

 lymph, etc., the muscle cells themselves containing no sodium at all. Such facts 

 necessitate in this case also the existence of a membrane impermeable to salts. 



According to Meigs and Ryan (1912, p. 411), however, the salts of smooth muscle are 

 present in a non-diffusible form, and these authors do not admit the presence of a semi- 

 permeable membrane. The evidence given is, I think, not very convincing. Smooth muscles 

 are stated, when immersed in hypotonic saline solution, to gain in weight according to a 

 different time law from that of striated muscle in the same conditions. This fact is readily 

 to be accounted for by a different amount of imbibition in the two cases. Imbibition may 

 play a relatively important part in smooth muscle, although as we have seen above (page 116), 

 it plays only an insignificant part in the case of striated muscle. Water taken in by imbibition 

 is not, of course, active osmotically, so that in order to balance a given external osmotic 

 pressure, more water must be taken in per unit time if part of it is inactive. Again, it is 

 said that, if smooth muscle is immersed in an isotonic solution of cane-sugar, it gains weight 

 much more rapidly than striated muscle does ; but we shall see presently that cane-sugar is 

 by no means an innocuous substance for many cells, and the more rapid gain of weight is what 

 would be expected if a certain amount of imbibition were taking place. It appears also that, 

 when smooth muscle is cut across, its potassium content diffuses out very slowly ; the possi- 

 bility of adsorption, or the formation of a new membrane on the cut surface, is not taken into 

 due consideration. These observers also regard the loss of potassium phosphate by ordinary 

 muscle in activity and its replacement as inconsistent with a semi-permeable membrane. But, 

 admitting the loss of phosphate, we shall see later that there is an increase of permeability in 

 the excited state and it may well be that the passage of salts takes place at this time. 



There are many other facts, of interest also on their own account, which 

 prove an impermeability to crystalloids. 



Bethe (1909) found that medusae, floating in sea water stained with neutral 

 red, stored the dye in their cells with the orange-red colour which it has in a 

 solution of neutral reaction. If hydrochloric acid were added to the water, so 

 as to give the dye in it a cherry-red colour, it was found that no change was 

 produced in the tint of the cells for several hours ; in fact, acid paralysis might 

 be caused, but no change in the colour of the cells could be seen, until they 

 were dead. The same thing was noticed with sodium hydroxide ; the cells did 

 not become yellow, the colour of neutral red in alkaline solution. 



From the experiments of O. Warburg (1910) on the eggs of a sea urchin, 

 the same fact, amongst others, was clearly made out. In this case, it was shown 

 that the absence of change of colour was really due to non-entrance of alkali, and 

 not to some fixed state of the dye making it inert to alkali, by taking an 

 alkali to which the cell membrane is known to be permeable, such as ammonium 

 hydroxide, in which case the colour became yellow almost instantly. 



The objection may be made that the chemical or adsorption compound of the dye with cell 

 structures may be less sensitive to sodium hydroxide than to ammonium hydroxide. This has 

 been dealt with by Newton Harvey (1913), who has shown that the adsorption compounds of 

 neutral red with various proteins, with lecithin, etc., are affected by these two alkalies in 

 exactly the same concentration. Moreover, when the sea urchin eggs are made actually per- 

 meable to sodium hydroxide, by the action of sea water saturated with chloroform, this alkali 

 changes the neutral red in the cells just as readily as ammonium hydroxide does. 



An important fact emerges from the above experiments of Bethe and Warburg. 

 That is, that acid and alkali can produce their characteristic effects without 

 entrance into the substance of the cell. This question will be referred to 

 again later. 



Jacques Loeb (1909), in investigating the effect of acids on the formation of 

 the fertilisation membrane in the eggs of the sea urchin, found that this effect 

 was not in proportion to the strength of the acids, but to their permeability or 



