Comparative Electro-Physiology: A Physico-Physiological Study

(fig. 371) that, owing to imperfect conductivity of the inter- vening tract, but little excitation reaches it. Excitation at S, however, distorts the molecules in its immediate neighbour- hood, in a certain direction, incipiently distorting others at a little greater distance in the same favourable way. A second stimulus is therefore transmitted a little further, bringing about the same predisposition still further on, Thus an im- proved conducting-path is made, in a substance formerly but.

an indifferent conductor, by the action of the stimulus itself. In this way transmitted excitation, at first relatively ineffec- tive, becomes increasingly effective (fig. 377). It is very interesting to note that I have obtained an effect exactly parallel in the case of nervous tissues. For example, when attempting to obtain the transmitted effect of ex- citation by mechanical response, in a vegetable or animal nerve in de- pressed tonic condition, the first series Fic. 377. Gradual Enhance- Of tetanising shocks would induce no RED oe Caen response. It would sometimes be } only after long repetition that con- ductivity would be gradually restored, as seen in the initiation and subsequent enhancement of responses given at the distant responding-point: - It may be that few phenomena connected with the response of living tissues, bring home to us, so effectively aS an experiment on a nerve-and-muscle preparation, the sense of the specific and mysterious character of the responsive manifestations of the living. The nerve, at its central termination, is locally excited by electric shocks, and some obscure impulse then passes through the long conducting tract to the muscle at the other end. Arriving there, this invisible nervous impulse initiates a new Series of events, which find expression in visible motile indications The work performed at the responding end may be out of all proportion to the strength of the stimulus imparted at the centre. It is as if the nervous impulse tapped a relay, and

set free a local store of latent energy. The conductor, moreover, is seemingly unlike the conductor in an electrical circuit, where the line wire and return wire must be periodically connected with terminals of an electro-motive source, for any message to be transmitted. In the nerve we have only a single conductor, without a return, an arrangement by which it would appear as difficult to send a message, as it would be to apply the two poles of a battery at the end of a single wire, in the expectation of a signal from the recorder at the far end. Inorganic matter again, is popularly regarded as susceptible only of impulses from the grosser physical forces, while the nerve—the vehicle of psychic impulses—is conceived of as_ played upon by forces of a finer order, ‘and as itself modifiable, by subtler influences, notably that of its own previous history,or memory. There are, as we know, some conditions which induce such changes in the nervous channel itself, that messages from outside, previously scarcely perceptible, are accentuated. Under opposite influences, again, the conduction of impulse is interrupted. Similar results are brought about by certain agents of a polar character, like the action of anode and kathode. Under electrotonic action the transmission of impulses through the nerve may be blocked, conduction being renewed as soon as the electric block is removed. Or electrotonic action, again, may be used for the opposite purpose, of accelerating the trans- mission of impulses. Nothing more convincing than such facts could have been urged in support of the hyper-physical character of the phenomena in question.

But the experiments which I have described, relating to the conduction of excitatory molecular changes in a piece of iron wire, show that parallel phenomena occur in the physical domain also; and in order to demonstrate this in a striking manner, I cannot do better than describe an arrangement which I have devised, and which may be taken as an artificial nerve-and-muscle preparation. This consists of a thin iron rod for the transmission of magnetic

excitation applied at one end, with a responding arrange- ment, to give motile indications, at the other. This latter consists of a secondary coil, which may be slipped over the responding point, being in series with some sensitive metallic powder in circuit with a galvanic recorder, and a voltaic cell as source of energy. The excitatory molecular dis- turbance transmitted through the conducting iron rod gives rise, on reaching the responding-point, to an_ electrical disturbance in the secondary coil connected with the motile indicator. This electrical disturbance causes secondary excitation of the sensitive substance, in consequence of which the electric conductivity of the particles becomes suddenly enhanced. By this ‘relay’ action the stored-up energy of the cell is suddenly released, with a consequent ‘induction of motile response in the galvanic recorder. It is thus seen that this motile response, initiated by the transmitted stimulus, need not be proportionate to its primary exciting cause, since it may possibly be much en- hanced by the amount of energy set free in the responding circuit itself. This transmission of excitation is liable, moreover, as in nerve, to be modified by subtle molecular changes induced in the conducting tract through which it takes place. Excitation may be arrested in the one case by an electrical block ; and in the other, similarly, we are able to stop the transmission of a message, by means of a magnetic block. It is by no gross physical restraint that the impulse is so arrested, but by invisible molecular distortion within the rod. Molecular freedom is next re- stored by the removal of- the magnetic block, and we find that the message, which, though constantly reiterated, was hitherto inhibited, is suddenly allowed to rush onwards and bring about the signal. ;

Anomalies of response—Explicable only from consideration of antecedent molecular changes— Continuous transformation from sub-tonic to hyper-tonic conditions—Two methods of inquiry, first by means of characteristic curves, second by progressive change of response—Abnormal response characteristic generally of A or sub-tonic state—Abnormal transformed into normal, after _ transitional B state—B state characterised by staircase response—Responses at C stage normal and uniform—aAt stages D and E responses undergo diminution and reversal— Responsive peculiarities seen during ascent of curve, repeated in reverse order during descent—All these peculiarities seen not only in living but also in inorganic substances, under different methods of observation— Elucidation of effect of drugs—Response modified by tonic condition and past history.

WE have seen that, normally, the phenomenon of response in living tissues is very definite’ There are other con- ditions, however, under which it is found to be modified or even reversed. These abnormal effects may be brought about, either by feeble stimulation, or by changes in the responding tissue itself. Thus, though moderate stimulus evokes normal negative response, a feeble stimulus will often be seen to induce the abnormal positive, and this is most easily observed in certain particular modifications of the tissue associated with sub-tonicity. The fatigue-changes due to excess of stimulation are also, curiously enough, effective in bringing about the same abnormalities of response.

It is open to-us to regard these anomalies as the result of obscure vital actions, and therefore incapable of further analysis. Or,since the phenomenon of response itself is admitted to be due to the molecular upset caused by stimulus, their origin may be looked for in the antecedent molecular condition of the responding substance. There is a school of investigators, again, who, appearing to discard the theory of vital action, in accounting for these changes, have substituted for it the hypothetical anabolic, or up-building, and catabolic, or down-breaking, chemical changes. And such assumptions have certainly the advantage of meeting every emergency, whether it be an expected effect or its direct opposite which occurs, for by their means it is always _ possible to make a reference to the one process or the other, whatever be the inconsistency involved.

- As regards the interminable controversy on the physical versus chemical nature of response-phenomena, I have already drawn attention to the fact that on the border-line between Physics and Chemistry it is impossible to make any sharp demarcation. Changes, in themselves undoubtedly molecular or physical, may be attended by concomitant changes of chemical activity. An example will perhaps make this clear. We may take, for instance, the photo- graphic action of light on a sensitive plate. This is re- garded as due to chemical dissociation or break-down. If this were so, however, the effect would be permanent. But, instead of this, the latent image is liable to disappear, and in a Daguerreotype plate the after-effect of light—that is to say, the persistence of the image—has a duration of a few hours only. Such images, moreover, due to the action of light, have been found to form themselves even on elementary and inert chemical substances like gold. Here, any chemical break-down, in the ordinary sense of the word, is out of the question.

Stimulus in general we have seen to induce molecular distortion, the persistence of which is dependent on the strength of the stimulus, and also on the power of self- recovery characteristic of the given substance. We have further seen a difference of electrical potential to be induced, as between molecularly strained and unstrained areas. When the substance, therefore, thus differentially acted upon, is placed in a suitable electrolyte, volta-chemical actions are

necessarily set up, by which material in one part may be accreted, and in another dissolved. In this way a positive or negative image may be developed. We have also seen, in the responses of living tissues, that while moderate stimulation induces one effect, the same stimulation, long continued, may cause the so-called fatigue- reversal, such reversals sometimes, in fact, becoming recurrent. It is interesting to note that in a similar fashion a photographic plate, subjected to various durations of exposure, will give either negative or reversed positive images, or recurrences of these." :

From such facts it is clear that for the elucidation of response and its variations, we must look to its molecular antecedents, and not to its secondary chemical or other consequences. If response phenomena in general, then, are determined by molecular conditions, as such, it follows that in order to unravel the anomalies which occur in - the response of living tissues, we must attempt to ascertain those conditions which induce any given variation of response in matter in general. That these phenomena are not peculiar to the response of living tissues, but take place in all matter under similar circumstances, is a fact which has been often reiterated in the course of previous chapters, and which I first pointed out in the course of my investigations on ‘Response in the Living and Non-Living,’ ?

In the work in question, referring to the occurrence of abnormalities in response, I said : ‘Calling a// normal response negative, for the sake of convenience, we observe its gradual modification, correspond- ing to changes in the molecular condition of the substance. Beginning with that case in which molecular modification is extreme, we find a maximum variation of response from the normal, that is to say, to positive. Continued stimulation, however, brings the molecular condition to normal, as

evidenced by the progressive lessening of the positive response, culminating in- reversion ‘to the normal negative. This is equally true of nerve and metal. In the next class of phenomena the modification of molecular condition is not so great. It now exhibits itself merely as relative inertness, and the responses, though positive, are feeble. Under continued stimulation, they increasé in the same direction as in the last case—that is to say, from less negative to more negative, this being the reverse of fatigue. This is evidenced alike by the staircase effect and by the increase of response. after tetanisation, seen, not. only in nerve, but also in platinum and tin. The substance may next be in what we call the normal condition. Successive uniform stimuli now evoke uniform and equal negative responses—that is to say, there is no fatigue. But after intense or long-continued stimulation, the substance is overstrained. The responses now undergo a change from -negative to Jess negative: fatigue, that is to say, appears. Again, under very much prolonged stimulation, the response may decline to zero, or even undergo a reversal to positive, a phenomenon which we shall find instanced in-the reversed response of retina, under the long continued stimulus of light.

‘We must, then, recognise that a substance may exist in various molecular conditions, whether due to internal changes or to the action of stimulus. .The responses give us indica- tions of these conditions. A complete cycle of molecular modifications can be traced, from the abnormal positive to the normal negative, and then again to positive, seen in reversal under continuous stimulation.’ ! It is the molecular cycle here referred to, with the con- comitant cyclic variation of response, that forms the subject of the present chapter.. I shall attempt to show that the various anomalies in-the response of living tissues, which were referred to in an earlier passage, may be elucidated

' In the above quotation I have, in accordance -with the convention which I now uniformly oe referred to normal response as negative, and abnormal as positive.—/. C. B _ by this consideration. I explained, im the first chapter of the present work, the fact that the molecular derangement of matter under stimulus might be studied by recording any one of several concomitant physical changes. -These are: (a) the change of form—contraction or expansion ; (3) the electro-motive change ; and (c) the variation of electric resistivity. By means of the first of these we investigated the responsive effects induced by stimulus in animal and vegetable tissues, and in the inorganic substance indiarubber. By the second, that of electro-motive variation, the excitatory change and its variations were studied in living tissues, animal and vegetable, and in inorganic bodies like metal wires. And, lastly, by variation of resistivity, we have obtained records of excitatory changes in living tissues, as also in masses consisting of metallic particles. In the last chapter, moreover, I have shown that the molecular responses of a magnetic substance may be recorded by means of appropriate magnetometric or galvanometric methods.

I shall now take up the question of the nature of those obscure molecular modifications which the response of a substance is found to undergo, and in consequence of which it exhibits variations either of intensity or of sign. The only conceivable reason for such changes would lie in some unknown transformation of the antecedent molecular con- dition. This being so, the next question is, whether we could possibly discover what these transformations are.

The properties of a substance at any given moment, we must remember, are not determined solely by the nature of that substance, but also by the energy which it possesses. It is obvious, for instance, that the responsive properties of matter, when its energy is depleted or its condition-is a-tonic, will be different from those of matter in a higher tonic-con- dition, and that there will be many gradations intermediate between the two. Thus, as a substance is gradually trans- formed, from a state of depletion to one of excessive energy, we~can see that, theoretically, there -might - be two possible ways of obtaining an insight into the progressive molecular

changes occurring in it. First of these would be the con- tinuous observation of the character of the replies made by the changing substance to the shock of stimulus, with the progressive modification of those replies. And the second method would lie in taking a continuous record of some property of the substance, as a whole, which was undergoing a concomitant change. In the first of these modes of scrutiny the information would be obtained by an inspec- tion of the varying responses. In the second, it would be arrived at by the examination of certain characteristic curves ;

Fic. 378. Characteristic Curve of Iron under increasing Force of Magnetisation and finally, if both these methods gave correct indications of the molecular state at the time being, then each particular response of the first method would be found to have its own place in the characteristic curve of the second. This characteristic curve will be best understood from a con- tinuous record of the induced molecular change occurring under the action of an increasing external force. The simplest example of this is afforded by the curve which shows the relation between induced magnetisation and inducing magnetic force (fig. 378). This induced magne- tisation, as will be understood, measures the amount of molecular distortion. A characteristic curve, essentially

similar, is obtained from filings of a substance belonging to the negative class under increasing electro-motive force (fig. 379). Taking first the substance in a low or indifferent condition, we find the curve in its earliest stage, A, to be almost horizontal. That is to say, the molecular distortion induced is here very slight. We next arrive, however, at a stage, B, which I shall call transitional, where increasing force induces change at a rapid rate. In the third stage, subsequent to this, there is a decline in the rate of change, the molecules now approaching their maximum distortion,

Fic. 379. Characteristic Conductivity Curve of Sensitive Metallic Particles belonging to Negative Class, under increasing Electro- motive Force These principal features are common to characteristic curves in general, slight deviations from the type being met with occasionally. In the cases given, for example, the substance starts from an indifferent condition. But it might have been in a still lower, or a-tonic, condition at starting. Under such circumstances I find that the tendency of the first part of the curve is to fall below the zero-line, crossing it, however, in an upward direction, at the transitional point B. When the curve, again, has reached the highest point, c, it may remain horizontal for a considerable time, or there may be a decline, owing, as we shall see, to fatigue.

If we take a cyclic curve, recording the effects. under increasing, followed by those under diminishing, force, it will be found that the forward and return portions of the curve do not in general coincide (fig: 380 a). Thus, when an increasing magnetising force starting from’ zero acts on an iron rod, and is brought back to zero, the condition of the rod at the end is not exactly the same as at the beginning. A certain amount of- molecular work, which is not reversible, has been done during the cycle.. A certain molecular distortion persists as an after-effect in residual magnetisation. Similarly, when

Fic. 380. Cyclic Curves of Magnetisation (2) and of Conductivity (4) metallic particles. are subjected to cyclic electro-motive varia- tion, an after-effect is found to persist in a change of con- ductivity. In substances belonging to the negative class the after-effect is one of enhanced conductivity ! (fig. 380 4). Referring again to that molecular condition of the substance which is represented by @ in fig. 378, we find that a new increment or accession of force will raise its condition to 4’. In this case the acting force has been continuously operative and continuously increasing. On the cessation of the acting foree, a substance possessing marked self-recovery will fall back from 6’ to 4 But if. there be a certain persistence of after-effect, then a

1 Bose, ‘On the Change of Conductivity of Metallic Particles under Cyclic Electro-motive Variation.’—7he Electrician, September 1901. stimulating force which had raised the substance to - 0’ would, when again applied, after a very brief interval, raise it to J’, and so on. That is to: say, the molecular effect would in this case be additive. Tetanisation - will thus give a curve bearing a great resemblance to the charac- teristic curve. This will be seen from the following record, obtained by magnetic tetanisation of steel (fig. 381), which bears so close a resemblance to the record of electrical tetanisation of nerve (cf fig. 313). Both these curves, again, resemble the typical characteristic curve seen in fig. 378. In

Fic. 381. Photographic Record of Magnetic Tetanisation of Steel, exhibiting Transient Enhancement of Response on Cessation all these we find that the curve rises, after a longer or shorter horizontality, in an abrupt manner ; that its rate of rise then undergoes a decline, the curve tending again to become horizontal ; after which fatigue-decline may be initiated. In the. photographic record of the magnetic tetanisation of steel (fig. 331), a remarkably suggestive phenomenon is ob- served. In that part of the tetanic curve which is horizontal the one-directioned molecular distortion, due to stimulus, is exactly balanced by the force of restitution. On the sudden cessation of tetanisation the state-of balance is disturbed, and we obtain here the remarkable occurrence of a_ brief overshooting, Or positive variation, in the curve, followed

by recovery. This is exactly parallel to the sudden enhancement of response in the retina on the cessation of tetanising light, or to the enhancement of response in the nerve when the tetanising electrical shock is suddenly withdrawn (pp. 428, 536). From the present experiment it will be seen that the suggested explanation of the pheno- menon, as due to anabolic or katabolic changes, is gratuitous. In responding substances, where the persistence of after-_ effect is relatively great, the successive shocks for the obtaining of the tetanic curve need not be repeated so quickly as where recovery is rapid. The shifting of the base-line of a series of even such responses as indicate incomplete tetanus, will give an indication of the form of the characteristic curve. The progressive molecular modification of a substance may thus be gauged, as already pointed out, in either of the two different ways—by progressive changes in the character of the response, or by means of the characteristic curve of the substance, And if both these, again, represent correctly the molecular condition of the material, we shall further find that definite parts of the characteristic curve have each their peculiar responsive features. In order to take these records ‘of the characteristic curve and corresponding responses of a substance, moreover, we may adopt any method that is convenient—mechanical, electro-motive, magnetic, or that of the resistivity variation. The feasibility of such records is obviously a matter of the extent of the change induced and the sensitiveness of the recording apparatus. Of the various methods here mentioned, it may be said that there are no particular sources of uncertainty to be guarded against in regard to variations of resistance, of magnetisation, or of length. But in the method of electro-motive variation, as the change to be recorded is relative, being measured against a neutral or indifferent point, some difficulty occurs in securing a point which is invariable. This may be done more or less per- fectly, however, by choosing an injured or killed point on the tissue for the second contact, in order that it may be subject to as little variation as possible from environmental changes.

‘We shall now proceed to the description of the distinctive characteristics of certain. molecular states, We may take first the case of ‘nerve, which gives different characteristic responses under different’ conditions; and here, employing the simplest mode of record—namély, the mechanical—we find, as already said; that, when it is cut off from all sources of energy, the specimen is apt°to fall into a condition of stowing sub-tonicity,, This is indicated in the mechanical

Fic. 382. Mechanical Response of Frog’s Nerve to successive equal Stimuli, applied at Intervals of One Minute The sloping line at the beginning shows growing elongation due to sub- tonicity, Stimulus here causes positive response. Fourth, fifth, and sixth responses are distinctly diphasic. Responses become normal and ‘increasingly negative’ after the seventh, with marked staircase increases. Molecular transformation is seen to be very rapid, above the

B point of transition. Record is a photographic reduction, half original size, of tracings obtained on smoked glass, record by an increasing abnormal elongation, as in fig. 382, given above. When the nerve is now subjected to the action of stimulus, its. tonic condition is gradually restored, progressing towards a normal excitatory condition. The molecular transformation involved here is at first expressed by growing retardation of the abnormal elongation, and afterwards by gradual contraction. At the point of trans- ition from positive to negative, or from elongation to