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TRANSMISSION OF ACTIVATION IN
OUS TYPE OF TRANSMISSION
point of stimulation and activates the whole. with its inorganic model, but rather a class The characteristic functional manifestation resemblance of a definite and unmistakable then appears-contraction in a muscle cell, kind; the inorganic process should exhibit motor reaction in a protozoon, cell division peculiarities which stamp it clearly as a pheand development in a resting egg cell, etc. nomenon of the same essential kind as the Conduction is in fact a widely general if not physiological process. If the comparison is a universal cell process. Excitation may thus be true one, the transmission of chemical intransmitted not only between different regions fluence to a distance in cells or nerve fibers of the same cell or cellular element but also and the transmission of similar influence in between different cells or elements which are the inorganic model should take place at in contact with one another; the transmission similar rates, be influenced similarly by exbetween neurones in the central nervous sys- ternal conditions, be initiated by the same tem and from a nerve to its muscle or other means, have the same external manifestations, terminal organ illustrates this type of conduc- and be dependent upon the same underlying tion. It is thus possible to distinguish be- physico-chemical factors. Just as the passage tween intracellular and intercellular conduc- of the pulse wave in an artery and that of a tion, although there is probably no essential distension wave in a simple elastic tube are difference between the two types.
both determined by general physical factors Physiological transmission of the kind de- common to both objects, so the transmission of scribed seems to have in it something myste- chemical or metabolic influence along a living rious and specifically vital; in fact the problem conducting element like a nerve should-in of the essential physico-chemical nature of the case of a valid comparison-depend upon nerve conduction—the type phenomenon of certain fundamental features of physico-chemthis class—is still regarded by most physiol- ical constitution present also in the inorganic ogists as unsolved, and apparently by many as model. Is there in fact any known general insoluble. The difficulty of the problem has class of non-vital physico-chemical phenomena been accentuated by the apparent lack of any to which we can thus assign the phenomenon close analogies with known inorganic proc- of protoplasmic conduction? esses. Comparisons with the electric current, In the stimulation of an irritable living with the transmission of mechanical influences structure by an external agent, the primary or such as elastic strain or vibration, and with releasing event is undoubtedly a surface procthe propagation of explosive waves or of germ- ess of some kind; the characteristic activation effects like crystallization in supersaturated response" of the whole irritable element solution, have all proved inadequate and often follows automatically upon this surface change. highly misleading. Yet it would seem that In most irritable cells any local mechanical or any phenomenon which is so universal in or- chemical alteration of the protoplasmic surface ganisms and upon which many of their most layer (or “plasma membrane"), or a slight characteristic activities directly depend-es- change in its electrical polarization due to an pecially in animals—must have some general electrical current, may cause excitation. There physico-chemical basis present also in inor- is little doubt, however, that the essential deterganic nature. The problem is to find some mining factors in any form of stimulation are simple and readily reproducible inorganic electrical; and that mechanical and chemical process, involving transmission of chemical in- stimuli excite the cell indirectly by means of fluence, which is similar in its most general the local electrical effects which they produce. features to the conduction process in living The stimulating agent alters locally the struccells, initiated under similar conditions, and ture or composition of the surface film; the dependent upon the same fundamental factors. state of electrical surface polarization is there What is to be looked for is not complete or changed; and the bioelectric circuit arising detailed identity of the physiological process tween altered and adjoining unaltered regions
completes the activation. This view at once Each of the areas of local chemical action thus explains why the electric current is the most represents an electrode-area in a local elecuniversal stimulating agent. It is well known trical circuit; and electrolysis at these areas that stimulation of any cell, by whatever is what determines the chemical changes there means induced, is always accompanied by an taking place. Now electrolysis is a process electrical variation of the cell surface, or cur in which the transmission of chemical inrent of action; and we find the same to be true fluence to a distance without transfer of mateof the propagation of the excitation wave. This rial is an essential and constant characteristic; last process, which is evidently essential to the the very flow of the current depends in fact stimulation of the cell as a whole, is appar upon this condition. Any electrochemical ently dependent upon the bioelectric circuit change at one electrode of a battery or other formed at the boundary between the active and electrical circuit due to chemical action necesinactive regions of the cell surface; that part sarily involves a corresponding change of a of the local current which traverses the still chemically opposite kind at the other elecinactive regions stimulates these electrically; trode. Oxidation, the general effect at the the regions thus secondarily excited act sim anode, thus involves simultaneous reduction ilarly upon the resting regions next adjoining; at the cathode; an oxidizing substance placed the process repeats itself automatically at each in contact with one electrode will thus innew active-inactive boundary as it is formed, stantly oxidize a reducing substance at the and in this manner the state of excitation other electrode. Spatial separation of the two spreads continually from active to resting regions is a matter of indifference except in regions. A wave of activation thus travels so far as it increases the electrical resistance over the surface of the element.1
of the circuit, thus retarding the rate of the If this theory of conduction is well founded, electrochemical process. The transmission of the chemical alteration of a surface film of the chemical influence between the electrodes material under the direct influence of local is automatic and instantaneous. electrical circuits would seem to be indicated This “ chemical distance action "3 suggests as the essential basis for the transmission. a possible basis for the protoplasmic type of Changes of this kind are in fact a frequent transmission, since distance action is a feaphenomenon at the surfaces of metals in con ture of all electrochemical circuits, including tact with solutions; and in a recent paper? I those present in local action at metallic surhave called attention to the many striking faces. If therefore it could be shown that the analogies between the effects of such local cell surface can act like a metallic surface the electrolytic action in metals and the effects of essential difficulties of the problem of protolocal stimulation in living cells. For example, plasmic transmission might be regarded as in the rusting of iron in aqueous solutions the
An inconsistency, however, appears formation of local electrical circuits between in the fact that the transmission of electrodifferent regions of the metallic surface is chemical influence in a circuit is instantaneous now generally recognized to be the chief
(i. e., 3 X 1010 cm. per sec.), while the most factor in the process. The surface layer of rapid protoplasmic transmission-in the motor metal is typically not homogeneous, but ex nerves of mammals-is only 120 meters per hibits local anodal and cathodal areas; at the second; again, the intensity of chemical disformer regions the ions of the metal enter tance action decreases with the distance besolution and are precipitated as oxide or car tween the electrodes, because of the increase in bonate, while nascent hydrogen and alkali are electrical resistance, while in the nerve impresumably formed at the cathodal regions. pulse there is normally no decrease in inten
sity (or “decrement") as the local change 1 Cf. Amer. Jour. Physiol., 1915, Vol. 37, p. 348; 1916, Vol. 41, p. 126.
3 Cf. Ostwald, Zeitschr. physik. Chemie, 1891, 2 Loc. cit., 1916.
Vol. 9, p. 540.
passes along the fiber. Such difficulties are striking examples are seen in the transmission only apparent, however; in nerve conduction of the state of activity over the surface of it is quite certain that an entirely new state of metals, especially iron, which have been activity is aroused at each successive region brought into the temporarily non-reactive or of the fiber as the impulse passes; and all of "passive" condition by immersion in strong the evidence indicates that the speed of trans- nitric acid (or other suitable oxidizing agent) mission is determined mainly by the sensi- and are then placed in dilute acid and made tivity and local rate of response of the nerve, to react. It has long been known that iron and not at all by the rate of transmission of which has been thus “passivated” becomes the electric current in the bioelectric circuit. resistant or refractory to reaction and (for exIt is probable that in the local bioelectric ample) no longer dissolves spontaneously when circuit set up by the initial stimulus the placed in dilute nitric acid (s. g. 1.20). But direct chemical influence of the current ex- if while immersed in the dilute acid it is tends for only a short distance, at most a few touched momentarily with a baser metal, or centimeters from the original site of stimula- with a piece of ordinary non-passive iron, it tion; but one of its effects is to originate a is at once "activated” and reacts vigorously new' and similar circuit in the adjoining with the acid until dissolved. The experiregions of the fiber; this process repeats itself ment is a striking one and easily performed. as already indicated, and in this manner the In my own demonstrations a piece of pure iron impulse spreads. The observed speed of the wire (No. 20 piano wire, bent at one end into a activation-wave has thus nothing to do with hook for handling) is passivated by immersion the speed of the purely electrochemical dis- in strong nitric acid (s. g. 1.42) for a few tance effect. What we seem to observe is a seconds, and is then placed (by means of a local electrical circuit which travels along the glass hook) in a flat dish containing dilute nerve together with the activation wave; but acid (s. g. 1.20). The wire if left undisturbed in reality there is a succession of new cir- remains bright and unaltered for an indefcuits, each of which automatically arises at inite time. If then it is touched at one end the boundary between resting and active re- with a piece of ordinary iron, or with zinc or gions as the front of the activation wave ad- another baser metal, the bright metallic sur
The relatively slow rate of movement face is at once darkened (through formation of the impulse and the absence of a decrement of oxide) and active effervescence begins; this may thus be understood.
change is transmitted rapidly, though not inThe rapid passage of a wave of chemical stantaneously, over the entire length of the decomposition (probably oxidative in nature wire; the velocity of transmission varies with and involving some structural change) over the conditions, and is of the order of 100 or the surface of the reacting element, followed more centimeters per second in this experiimmediately by a reverse change which re- ment. The wave of activation may also be stores the original or resting condition, is initiated mechanically, e. 9., by bending the what appears to take place in a nerve or other wire or tapping it sharply with a glass rod; or living structure during conduction. Asso- chemically, e. g., by contact with a reducing ciated with the chemical process is a local susbtance such as sugar; or electrically, e. 9., electrical circuit by whose electrolytic action by making the wire (while immersed in the the chemical change is apparently determined. acid) the cathode in any battery circuit (of Have we examples of similar processes in in- two or more volts potential), preferably with organic systems? It appears in fact that this
another piece of passive iron wire as anode; general type of process is not unusual in metals
o For a recent extended study of the passive in contact with solutions. Especially clear and
state in metals with full references to the literature, 4 Cf. Amer. Jour. Physiol., 1914, Vol. 34, p. 414; cf. Bennett and Burnham, Jour. Physical Chem., Vol. 37, p. 348.
1917, Vol. 21, p. 107.
the cathodal wire is instantly activated, while the same effect is thus evident. The parallel the anodal wire remains unchanged. Acti to the living irritable tissue is plain; local vation with the electric current is thus alteration of the protoplasmic surface film typically a polar phenomenon, just as is the produces effects of a closely comparable naexcitation of a living irritable element like a ture, which spread in an analogous manner nerve.
by means of the local electrical circuits Activation by contact with active iron or a formed. We are thus enabled to understand baser metal is in reality an instance of elec why any rapid local alteration of the cell trical activation, the activating metal form surface may activate the whole cell-in other ing the anode of the local circuit arising at words why the cell is so characteristically the region of contact. At the local cathode, “irritable.” The iron wire in its passive state i. e., the adjoining passive iron, the metal is may be compared to the irritable living eleat once activated, and the effect spreads in the ment in a state of rest. The state of inmanner already indicated by means of the activity continues in both cases only so long circuit which automatically arises at the as the surface layer is intact and homogeneous. boundary between active and passive areas. The reason why the whole cell (or the whole Any metal which thus activates by contact iron wire) responds completely to a local stimmust be of such a nature that the passive iron ulus is simply because transmission over the becomes the cathode of the local circuit entire surface follows automatically and informed. A metal which is nobler than passive evitably upon local activation. The “all-oriron, like platinum, not only does not cause ” behavior thus becomes intelligible. activation, but it renders the iron locally more Under normal conditions an irritable nerve resistant to activation; thus the passage of or muscle returns spontaneously to an inthe activation wave may be blocked by the active or “resting state after stimulation, contact of a platinum wire. This latter effect and for renewal of activity a second stimulus depends upon the formation of a local circuit is required. The resting condition thus repreof the reverse orientation, the iron becoming sents a condition of equilibrium, which is anodal, a condition which furthers passivation temporarily disturbed by the stimulating and hinders activation. Active iron is a base agent. The same is true of the passive conmetal in relation to passive iron, being more dition of iron in strong solutions of nitric negative that the latter by ca. 0.75 volt in acid. In weaker solutions, of s. g. 1.20 and 1.20 HNO3; hence when any region of a pas less, the reaction once initiated continues unsive wire is rendered active it immediately checked until all of the iron is dissolved; but activates the adjoining areas.
in stronger solutions the reaction is temporary In passivation the surface layer of the iron and the metol returns spontaneously to the is modified in a peculiar manner, apparently passive condition. A wave of temporary activby the formation of a thin resistant layer of ity thus sweeps over the surface of a passive higher oxide. Any condition that interrupts iron wire which is activated (e. g., by touchlocally this surface film of altered iron forms ing with zinc) in nitric acid of s. g. 1.25 or necessarily a local circuit by whose action the higher; the state of local activity lasts in whole metal is activated in the manner just such a solution for a brief period only, which described. Apparently at any cathodal area is the shorter the higher the concentration of the surface film of oxide is reduced to metallic the acid. An interesting gradation of effect iron; contact of a reducing substance has a may thus be shown by activating a series of similar effect; while a mechanical agent passive wires in different dilutions of strong breaks the continuity of the film and exposes (s. g. 1.42) acid, e. g., 90, 80, 70, 60 and 55 the unaltered iron beneath, thus forming the volumes per cent. (i. e., 90 c.c. 1.42 HNO3 local circuit. The reason why mechanical, plus 10 c.c. water, etc.). When a wire imchemical and electrical influences all produce mersed in pure 1.42 acid is touched at one end