968 



SCIENCE 



[N. S. Vol. XXXVII. No. 965 



of permeability, as I shall shortly point out. 

 Evidence from various sides thus proves 

 the participation of the plasma-membranes 

 in the stimulation-process. Just why a 

 change in the permeability and electrical 

 polarization of the plasma-membrane 

 should influence so profoundly the meta- 

 bolic and other activities of the cell is nat- 

 urally a far-reaching question requiring 

 further investigation, but there are many 

 reasons for believing that the primary or 

 initiatory phase of the stimulation-process 

 is a change of this nature. 



Let us return now to the question of why 

 anesthetics interfere with the stimulation- 

 process. In the first place they can be 

 shown experimentally to interfere with 

 both of the above characteristic mani- 

 festations of stimulation, (1) the action- 

 current and (2) the change of perme- 

 ability. If these are the critical or primary 

 events, on which the other effects following 

 stimulation depend, it is evident that sup- 

 pression of these must involve a suppres- 

 sion of the entire series of processes result- 

 ing from stimulation, including the oxida- 

 tions, the contraction-changes and the other 

 special features of the response. 



That the action-current as well as the 

 mechanical response of a muscle is sup- 

 pressed by anesthetization has long been 

 known. In nerve also anesthesia abolisht s 

 the action-current. Now, on the foregoing 

 hypothesis, the electrical vax'iation is the 

 expression of some alteration in the 

 plasma-membrane, involving a temporary 

 increase of permeability. Hober has found 

 that potassium salts, which deprive nerves 

 of irritability and render them locally neg- 

 ative, cause at the same time a visible alter- 

 ation in the axis-cylinders; these structures 

 swell and stain more diffusely; he found 

 further that these effects are checked or 

 prevented if the nerves are first anesthet- 

 ized with ethyl urethane. Experiments on 



voluntary muscle gave analogous results. 

 If a frog's muscle is partly dipped into an 

 isotonic solution of a potassium or rubi- 

 dium salt the tissue contracts somewhat 

 and becomes locally negative; this effect is 

 also inhibited or retarded in the presence 

 of an anesthetic." If the local negativity is 

 the expression of a change produced by the 

 salt in the colloids of the plasma-membrane, 

 rendering the latter more permeable than 

 before, Hober 's results indicate that the an- 

 esthetic decreases the susceptibility to such 

 changes of permeability. If this is the case 

 we can partly understand why the anes- 

 thetized tissue becomes less susceptible to 

 stimulation, since stimulation involves an 

 increase of permeability. 



Quite recently at Woods Hole I have in- 

 vestigated the question of the nature of an- 

 esthetic action in a somewhat different man- 

 ner, using an organism which seems un- 

 usually well adapted to throw clear light 

 on this subject. If an anesthetic acts by so 

 modifying the plasma-membrane of the ir- 

 ritable cell as to render diiificult or impos- 

 sible the rapid variations of permeability 

 which are essential to stimulation, it ought 

 to act similarly on other cells, i. e.. it should 

 protect these cells also against the action 

 of permeability-increasing substances or 

 agencies. If an organism can be found 

 whose cells undergo immediate and obvious 

 increase of permeability under conditions 

 which at the same time cause stimulation, 

 it should become possible to determine 

 whether suppressing the stimulating action 

 of a given agency is equivalent to a suppres- 

 sion of its permeability-increasing action. 

 The two effects ought to show a definite 

 parallelism if the above hypothesis is 

 well-based. The organism which I have 

 used is the larva of the marine annelid 

 Arenicola cristata. This organism shows 



»C/. Hijber, Pfluger's ArcUv, 1907, Vol. 120, 

 p. 492. 



