September i6, 1915] 



NATURE 



69 



result of this is increased permeability and excitation 

 resulting therefrom. 



I referred previously to the electrical change in 

 excitable tissues and its relation to the cell mem- 

 brane. It was, I believe, first pointed out by Ostwald 

 and confirmed by many subsequent investigators, that 

 in order that a membrane may be impermeable to a 

 salt it is not a necessary condition that it shall be 

 impermeable to both the ions into which this salt 

 is electrolytically dissociated. If impermeable to one 

 only of these ions, the other, diffusible, ion cannot 

 pass out beyond the point at which the osmotic pres- 

 sure due to its kinetic energy balances the electro- 

 static attraction of the oppositely charged ion, which 

 is imprisoned. There is a Helmholtz double layer 

 formed at the membrane, the outside having a charge 

 of the sign of the diffusible ions, the inside that of 

 the other ions. Now, suppose that we lead off from 

 two places on the surface of a cell having a membrane 

 with such properties to some instrument capable of 

 detecting differences of electrical potential. It will be 

 clear that we shall obtain no indication of the presence 

 of the electrical charge, because the two points are 

 equipotential, and we cannot get at the interior of the 

 cell without destroying its structure. But if excitation 

 means increased permeability, the double layer will 

 disappear at an excited spot owing to indiscriminate 

 mixing of both kinds of ions, and we are then prac- 

 tically leading off from the interior of the cell, that is, 

 from the internal component of the double layer, while 

 the unexcited spot is still led off from the outer com- 

 ponent. The two contacts are no longer equipotential. 

 Since we find experimentally that a point at rest is 

 electrically positive to an excited one, the outer com- 

 ponent must be positive, or the membrane is permeable 

 to certain cations, impermeable to the corresponding 

 anions. Any action on the ceil such as would make 

 the membrane f)ermeable, injury, certain chemical 

 agents, and so on, would have the same effect as the 

 state of excitation. If we may assume the possibility 

 of degrees of permeability, the state of inhibition might 

 be produced bv decrease of permeability of the mem- 

 brane of a cell, which was previously in a state of 

 excitation owing to some influence inherent in the cell 

 itself or coming from the outside. This manner of 

 accounting for the electromotive changes in cells is 

 practically the same as that given by Bernstein. 



It will be found of interest to apply to secretory cells 

 the facts to which I have directed your attention. If we 

 suppose that the setting into play of such cells is 

 associated with the production of some osmotically 

 active substance, together with abolition of the state 

 of semi-permeability of the membrane covering the 

 ends of the cells in relation with the lumen of the 

 alveolus of the gland, it is plain that water would 

 be taken up from the lymph spaces and capillaries 

 and escape to the duct, carrying with it the secretory 

 products of the cells. This process would be continu- 

 ous so long as osmotically active substances were 

 formed. Such a process has been shown by Lepeshkin 

 to occur in plants, and we have also evidence of in- 

 creased permeability during secretory activity in the 

 gland cells of animals. From what has been said pre- 

 viously, it is evident that electrical differences would 

 show themselves between the permeable and semi- 

 permeable ends of such cells, as has been found to be 

 the case. 



As a modifiable structure, we see the importance of 

 such a membrane as that described if it takes part in 

 the formation of the synapse between neurones. The 

 manifold possibilities of allowing passage to states of 

 excitation or inhibition and of being affected by drugs 

 will be obvious without further elaboration on my 

 part. 



NO. 2394, VOL. 96] 



Enough has already been said, I think, to show 

 the innumerable ways in which phenomena at phase 

 boundaries intervene in physiological events. Indeed, 

 there are very few of these, if any, in which som^ 

 component or other is not controlled by the action of 

 surfaces of contact. But there is one especially impor- 

 tant case to which I may be allowed to devote a few 

 words in conclusion. I refer to the contractile process 

 of muscle. It has become clear, chiefly through the 

 work of Fletcher, Hopkins, and A. V. Hill, that what 

 is usually called muscular contraction consists of two 

 parts. Starting from the resting muscle, we find that 

 it must have a store of potential energy, since we can 

 make it do work when stimulated. After being used 

 in this way, the store must be replenished, since energy 

 cannot be obtained from nothing. This restoration 

 process is effected by an independent oxidation reaction, 

 in which carbohydrate is burnt up with the setting 

 free of energy which is made use of to restore the 

 muscle to its original state. Confining our attention 

 for the moment to the initial, contractile, stage, the 

 essential fact is the production of a certain amount 

 of energy of tension, which can either be used for the 

 performance of external work or be allowed to become 

 degraded to heat in the muscle itself. It was Blix who 

 first propounded the view that the amount of this 

 energy of tension is related to the magnitude of certain 

 surfaces in the muscle fibres. But the fact was 

 demonstrated in a systematic and quantitative manner 

 by A, V. Hill. He showed, in fact, that the amount 

 of energy set free in the contractile process is directly 

 related to the length of muscle fibres during the 

 development of the state of tension. In other words, 

 the process is a surface phenomenon, not one of 

 volume, and is directly proportional to the area of 

 certain surfaces arranged longitudinally in the muscle. 

 This same relationship has been shown by Patterson 

 and Starling to hold for the ventricular contraction 

 of the mammalian heart and by Kosawa for that of 

 the cold-blooded vertebrate. It appears that all the 

 phenomena connected with the output of blood by the 

 heart can be satisfactorily explained by the hypothesis 

 that the energy of the contraction is regulated by the 

 length of the ventricular fibres during the period of 

 development of the contractile stress. The degree of 

 filling at the moment of contraction is thus the deter- 

 mining factor. 



That surface tension itself may be responsible for the 

 energy given off in muscular contraction was first 

 suggested by Fitzgerald in 1878, and it seems, from 

 calculations made, that changes at the contact surface 

 of the fibrillae with the sarcoplasm may be capable of 

 affording a sufficient amount. The difficulties in 

 deciding the question are great, but, in addition to the 

 facts mentioned, there is other interesting evidence at 

 hand. It has been shown, by Gad and Heymans, 

 by Bernstein and others, that the contractile stress 

 produced by a stimulus has a negative temperature 

 coefficient. Within the limits of temperature between 

 which the muscle can be regarded as normal, this 

 stress is the greater the lower the temperature. The 

 same statement was shown by Weizsacker (working 

 with A. V. Hill) to hold for the heat developed in the 

 contractile stage. Now, of all the forms of energy 

 possibly concerned, that associated with phase boun- 

 daries is the only one with a negative temperature 

 coefficient. .Another aspect of this relation to tem- 

 perature is the well-known increase of the tonus of 

 smooth muscle with fall in temperature. 



It is tempting to bring into relation with the chanee 

 in surface tension the production of lactic acid. In 

 fact, this idea was put into a definite statement bv 

 Haber and Klemensievich in iqoq in a frequently 

 quoted paper on the forces present at phase boundaries. 



