248 



SCIENCE 



N. S. Vol. XXX. No. 764 



higher concentrations they stimulate strongly, 

 cause visible increase of permeability, and 

 show pronounced toxicity. It would thus ap- 

 pear that marked increase of permeability, if 

 prolonged for more than a short time, is 

 highly injurious to cells — ^presumably on ac- 

 count of the diffusion of essential protoplasmic 

 constituents to the exterior and the resulting 

 chemical disorganization. Decrease of per- 

 meability, on the other hand, can have no such 

 injurious effect, but merely checks inter- 

 change of material across the plasma mem- 

 brane for the time being. 



In isotonic sugar solutions muscular con- 

 tractility is gradually lost. On transfer to 

 solutions of various electrolytes contrac- 

 tions return. Of the pure solutions of the 

 alkali salts the most favorable in restoring 

 contractility are those of sodium ; lithium and 

 caesium, while less favorable, resemble sodium 

 in their general action; rubidium and potas- 

 sium produce temporary contractions, but are 

 much more toxic than the others. The order 

 of increasing favorability for the cations is 

 thus : K and Eb < NH, <Li < Cs < Na. The 

 various sodium salts vary in their action ac- 

 cording to the nature of the anion; the order 

 of increasing favorability for anions is: 

 I<Br<]Sr03 (and ClOJ <Gl<HPO,<C,Hp,< 

 S0,<C00CH3. Of the alkali earth chlorides 

 MgCl, produces no return of contractions; 

 CaClj and SrCl^ cause slight contractions 

 lasting some time; BaClj almost immediately 

 destroys all muscular contractility. 



In explanation of the above effects it is as- 

 sumed that in the non-electrolyte solution the 

 normal permeability is decreased; hence the 

 inhibitory or anesthetic action. The above 

 electrolytes, by their action on the colloids of 

 the plasma membrane, increase the permea- 

 bility of the latter and so stimulate. On this 

 interpretation, any substance which alters the 

 plasma membrane in the direction of in- 

 creased permeability should iyso facto restore 

 contractility in larvag from sugar-solution. 

 It was found that weak solutions of acids 

 (HCl, H,SO„ HCOOCH3 in concentrations 

 of n/8,200 to 71-/12,800) in isotonic sugar solu- 

 tions restore almost normal contractions for 

 a certain time. Acid causes also marked in- 



crease in the state of tonic muscular contrac- 

 tion. Alkali, on the other hand, has little 

 power of restoring contractility, and induces 

 decrease of muscular tone or lengthening. 

 Weak acid thus appears to increase and alkali 

 to decrease the permeability of the plasma 

 membranes in larvae from sugar solution. 



Experiments on the influence of different 

 electrolytes in restoring contractility in larvae 

 from isotonic MgClj solution gave results es- 

 sentially similar to the above, with the differ- 

 ence that the restorations of contractions by 

 pure solutions of the above electrolytes is, as 

 a rule, less readily effected. Presumably 

 MgCl, solutions decrease the normal permea- 

 bility to a greater degree than sugar; anes- 

 thesia appears more rapidly and is more pro- 

 found in solutions of this salt than in those 

 of dextrose or other sugar. 



The question why increase of permeability 

 should correspond to stimulation and de- 

 crease to inhibition is answered in essentially 

 the following manner. It is assumed that 

 during periods of increased permeability the 

 loss of carbon dioxide from the cell will be 

 more rapid than normal; the energy-yielding 

 oxidative reactions of which this substance is 

 the end-product are thus accelerated as a 

 direct consequence of the increased rate of 

 removal of the reaction-product from the 

 system; hence the increased contractile ac- 

 tivity or other energy manifestation during 

 stimulation. Conversely, decrease of the 

 normal permeability means decreased loss of 

 carbon dioxide and hence retarded oxidation 

 and energy-production; stimulation is more 

 difficult at such times because of the greater 

 difficulty of increasing the permeability to the 

 critical degree required. This general view 

 ascribes primary importance to the plasma 

 membrane as probably the chief means by 

 which the velocity of the oxidative energy- 

 yielding reactions in the cell is varied. The 

 promptness and vigor of the response to 

 stimulation in highly irritable and active 

 tissues like muscle are to be regarded simply 

 as evidence of the high velocity with which 

 the energy-yielding process, when unimpeded 

 by the accumulation of reaction-products, 

 proceeds in such cells. The grounds of this 



