138 PRINCIPLES OF GENERAL PHYSIOLOGY 



protoplasm, it will readily be understood how important are changes in the 

 permeability of the membrane to these substances. That such changes occur is 

 indicated, amongst other facts, by the experiments of M'Clendon (1912, 2), who 

 found in excited muscle an increase of electrical conductivity, an index of increased 

 permeability to ions, such as we have seen to happen in Laminaria under the 

 influence of substances which increase the permeability of the cells. 



It might be thought, perhaps, that the separation of electrolytes from an adsorbed state, 

 owing to diminution of the active surface of the colloids in the cell by aggregation, as 

 suggested by Macdonald (1909, p. 44), would account for this. But we know that the cell 

 membrane is, under normal conditions, impermeable to ions, and acts as a non-conductor, so 

 that increased production of ions inside the cell, apart from increased permeability of the 

 membrane, would have no effect on the electrical conductivity of the tissue. 



Lillie (1911), also, has brought forward evidence to show that all agents which 

 cause increased permeability of the cell membrane act in an exciting manner. 

 This is very noticeable in the case of the larva of Arenicola, which contains 

 a yellow pigment to which the membrane is normally impermeable. When 

 placed in pure sodium chloride, isotonic with sea water, the cells become tonically 

 contracted, while at the same time pigment leaves them. This action of sodium 

 chloride is prevented by calcium or magnesium ions, just as the increased per- 

 meability of Laminaria produced by sodium ions is prevented by calcium. 

 Further discussion of the mechanism of muscular contraction will be found in 

 Chapter XIII. One interesting consequence may be noted here. If the state 

 of capability of being exeited to contraction is connected with the semi-permeability 

 of the membrane, it follows that when this state is changed into one of permeability 

 the cell will be inexcitable as long as the state lasts; hence the "refractory period." 



The observations of PfefFer (1873) on the movements of the sensitive plant 

 showed their cause to be the sudden disappearance of turgor in the cells of the 

 pulvinus, due to loss of semi-permeability and, therefore, of osmotic pressure, due 

 to escape of osmotically active substances, so that water also is pressed out. 



Narcosis. There is a group of substances which act on living cells in such 

 a way as to abolish temporarily those activities which we regard as manifestations 

 of life. These are called " narcotics " or " anaesthetics." The former name means 

 " making numb " or paralysing, while the latter obviously refers to abolition of 

 conscious sensation, so that, in general use, the former is used to apply to the 

 abolition of all forms of protoplasmic activity, including those of the nervous 

 system, while the latter, strictly speaking, should refer only to consciousness. 

 But, in point of fact, the substances themselves form one and the same group and 

 the names are frequently used interchangeably. 



As first pointed out by Hans Meyer (1899) and by Overton (1901), in- 

 dependently, the intensity of the narcotic action of a substance stands in relation 

 to its partition coefficient between fats or lipoids and watery liquids ; the more 

 soluble it is in the former, the greater its effect. Now, although this fact shows 

 how a narcotic obtains access to the interior of a cell, it does nothing more in 

 explanation of its action than to suggest that it is in some way exerted on the 

 boundary membrane. As pointed out above, the greater solubility in the 

 membrane would only entail a greater degree of activity if this were due to some 

 direct action on the membrane itself. The concentration in the water phase of 

 the cell would not be increased by mere increase of solubility in the membrane 

 alone. 



What evidence, then, have we as to the action of narcotics on the permeability 

 of this membrane ? 



As pointed out by Lillie (1912, 1), the property of rendering cells temporarily 

 irresponsive to stimuli belongs to the most diverse classes of chemical compounds. 

 The action of isotonic cane-sugar on muscle (see page 125 above) may be mentioned. 

 At the same time, the particular group known as " anaesthetics," par excellence, 

 such as ether, chloroform, alcohol, etc., are characterised by special activity of 

 this kind, which seems undoubtedly to be connected with lipoid solubility. On 

 the other hand, the mere fact of lipoid solubility does not make a substance an 

 anaesthetic. 



