May 16, 1913] 



SCIENCE 



765 



anesthesia to a modification of the lipoids. 

 But a reversible loss of irritability similar in 

 all essential respects to anesthesia may be in- 

 duced by substances which have no specific 

 relation to lipoids — as salts of magnesium or 

 calcium, acids in low concentration, non-elec- 

 trolytes like sugar — and also by the electric cur- 

 rent (anelectrotonus). From these facts we 

 must infer that although a change of state in 

 the cell-lipoids may induce anesthesia it is not 

 the essential change. Some other more general 

 process is involved. What is the nature of 

 this process? 



In studying the conditions of chemical stim- 

 ulation in the larva of Arenicola — a free- 

 swimming annelid trochophore, 0.3 milli- 

 meters long and abundant at Woods Hole — I 

 was struck with the fact that solutions which 

 stimulate the musculature powerfully, causing 

 strong and persistent shortening to half the 

 normal length, invariably cause an immediate 

 and marked exit of pigment from the body 

 cells. Among such solutions are pure isotonic 

 solutions of sodium and potassium salts. The 

 cells of the larvae contain a yellow water-sol- 

 uble pigment, which on death, or under other 

 conditions associated with increased permea- 

 bility of the plasma membranes (action of 

 cytolytic substances, as saponin), diffuses into 

 the medium and colors the latter a bright yel- 

 low. This pigment thus serves as a convenient 

 indicator of permeability- increase. The strong 

 stimulation caused by isotonic ISTaCl solution 

 is thus associated with a marked permeability- 

 increasing action. This is equivalent to a 

 cytolytic or toxic action, for definite toxic ef- 

 fects, as shown by breakdown of cilia and fail- 

 ure of the larvae to revive completely on re- 

 turn to normal sea-water, always follow even 

 brief exposure to the pure NaCl solution. 

 The stimulating, permeability-increasing and 

 cytolytic actions of the solution thus show a 

 definite parallelism. 



Conditions that prevent the immediate stim- 

 ulating action also prevent the permeability- 

 increasing and toxic action. Addition of a 

 little calcium or magnesium chloride, e. g., to 

 the NaCl solution has this effect. In such 



mixed solutions there is little or no immediate 

 stimulation or loss of pigment and the toxic 

 action is greatly diminished. Stimulationand 

 permeability-increase, with the associated 

 toxic or cytolytic action, are thus simultane- 

 ously prevented by the calcium or other an- 

 tagonistic salt. 



Similar effects are seen if the organisms are 

 briefly treated with magnesium chloride previ- 

 ously to being brought into the NaCl solution. 

 Isotonic MgCl^ solution causes neither stimu- 

 lation nor loss of pigment. The musculature 

 is rapidly anesthetized in this solution, and 

 the animals remain rigid and without con- 

 traction, swimming slowly by the cilia which 

 remain active. If the larvie are then trans- 

 ferred to to/2 NaCl no immediate effect is 

 seen. Stimulation and loss of pigment are en- 

 tirely absent, and correspondingly there is 

 little immediate toxic action. The treatment 

 with MgClj has a protective or anti-cytolytic 

 as well as an anesthetic or anti-stimulating 

 (desensitizing) effect. 



Similar effects are produced by lipoid-sol- 

 vent anesthetics. Larvae exposed to a 0.7 v. per 

 cent, solution of ether in sea-water are rapidly 

 anesthetized. If then they are brought sud- 

 denly into pure to/2 NaCl containing the same 

 proportion of ether, no stimulation or permea- 

 bility-increase is seen, and the toxic action is 

 diminished as before; i. e., recovery on return 

 to sea-water is much prompter and more com- 

 plete than after similar exposure to pure to/2 

 NaCl without previous anesthetization. Di- 

 rect transfer from normal sea-water to ether- 

 containing salt-solution also causes little or no 

 stimulation or loss of pigment. The anti- 

 stimulating action in this case also is associ- 

 ated with or involves a marked anti-toxic ac- 

 tion. 



I have performed similar experiments with 

 a large number of other anesthetics with the 

 same general results.' In those concentrations 

 which in sea-water produce typical reversible 

 anesthesia, the anesthetic checks or prevents 

 the immediate stimulating action of the salt 



^For a detailed account of these experiments 

 cf. American Journal of Physiology, 1913, Vol. 31, 

 pp. 264 seq. 



