Comparative Electro-Physiology: A Physico-Physiological Study

The critical point of reversal would in this instance appear to be slightly below 1 volt, in the case of the kathode, while in that of the anode, it was at 1 volt, or slightly above. The effect observed at the extreme points were the same in all cases. Individual differences were concerned only with the exact point of reversal. Thus the point of reversal for the kathode varied in different cases between ‘6 and 1 volt; whereas with the anode it varied from 1 to 1°5 volt. Ina. subsequent chapter, this phenomenon of reversal of sensation under varying intensities of E.M.F., when other forms ot stimulus are applied, will be studied in more detail. It may be stated here, however, that though the critical point of reversal varies to some extent with different individuals, and under different forms of stimulation, yet the law holds good that the excitatory effects induced by moderate E.M.F. are exactly reversed under feeble.

The main results regarding this opposition of the effects of feeble and strong E.M.F. may be still better demonstrated by the method of successive contrasts. In the last experi- ments, a long course of observations on the same individual, would be liable to fatigue the tissue. Moreover, the fine gradation of the changes induced is not calculated to exhibit the contrasts involved in their full intensity. Having, then, determined, from the previous experiments, that an E.M.F. of ‘5 volt and another of 2 volts were opposed in their excitatory effects, I now made special arrangements for applying these two intensities of E.M.F. alternately. For this purpose, I arranged a potentiometer which gave an E.M.F. of 2 volts between L and N (fig. 359), and of ‘5 volt between Land M. The end, L, was connected with the wound-spot by means of a non-polarisable electrode. A distant indifferent point, say on the surface of the finger, was connected with a double key KK’. When kK’ was pressed, ‘5 volt was applied, and when K, 2 volts. Further, by means of a reversing-key, P, the wound-spot could be made either anode or kathode at will. In this way, first making the wound-spot anode, I applied alternately the

E.M.F. of ‘5 and of 2 volts respectively. The lower voltage now gave rise to intense excitatory pain. On the cessation of the current the normal smarting sensation, due to salt, was restored, and on now applying 2 volts, this slight irritation was superseded by a sensation of soothing. This result was found to be repeated many different times. The kathodic effect was next put to the test, and found to induce responsive sensations exactly the reverse. The application of *5 volt caused a soothing sensation, due to depression of excitability. An E.M.F. of 2 volts, on the other hand, induced an increase of excitability, with con- sequent pain. |

METHOD OF SUCCESSIVE CONTRASTS TO SHOW REVERSAL OF SENSATION Wound-spot anode Wound-spot kathode E.M.F. ‘5 volt _ E.M.F. 2 volts E.M.F. of ‘5 volt E.M.F. of 2 volt Intense pain Soothing Soothing Painful From these experiments, then, it will be seen that during the passage of the current, and when the E.M.F. is low, it is the anode which increases the excitability, and the kathode which depresses. Pfliiger’s Law is thus seen not to be universally applicable, but to be true only within certain limits, the very reverse of this law holding good, in the case of excessively high, and in that of low E.M.F. The demonstration which has just been given of the latter of these two facts, is independently borne out by the results of electrotonic variations of excitability in nerves, described in the last chapter, where we saw that, with moderately feeble E.M.F., excitability was enhanced by the anode and depressed by the kathode.

It will thus be seen that polar variations ot excitability are not always the same, but differ in character, according as the intensity of the acting E.M.F. is moderate or low. The great significance of this fact is apparent, with regard to the medical application of electricity, since the failure to recog- nise that reversal of effects which is to be expected under a feeble E.M.F. might here lead to a result the very opposite of that intended. It has thus been shown that Pfliiger’s Law of the Polar Variation of Excitability is not universally applicable. It fails when the E.M.F. is either too high or too low, the effects observed under these circumstances being precisely. the opposite of those enunciated by Pfliiger. Under a low E.M.F. then, it is the anode which enhances the excitability, depression being induced by the kathode. This important fact, and the further fact that with low E.M F. conductivity is increased in the direction of the rising electrical potential, and depressed in that of the falling potential, will be found to explain all the varied electrotonic phenomena of nerves described in the previous chapter.

Two opposite responsive manifestations, negative and positive—Such opposite re- sponses induced by polar effects of currents of different signs—Arbitrary nature of term ‘excitatory ’—Pro-excitatory and anti-excitatory agents—Molecular distortion under magnetisation in magnetic substances—Different forms of re- sponse under magnetic stimulation—Mechanical, magneto-metric, and electro- motive responses— Uniform magnetic responses—Response exhibiting periodic groupings—Ineffective stimulus made effective by repetition—Response by resistivity-variation—Molecular model—Response of inorganic substance to electric radiation—Effect of rise of temperature in hastening period of re- covery and diminishing amplitude of response—Sign of response reversed under feeble stimulation—Conduction of magnetic excitation—The Magnetic Con-

- ductivity Balance—Effect of A-tonus and K-tonus, on excitability and con- ductivity— Conducting path fashioned by stimulus—Transmission of excitation temporarily blocked in iron wire, as in conducting nerve—Artificial nerve- and-muscle preparation, IT is admitted that the excitation of living tissues is brought about by some kind of molecular disturbance, and that the passage of this molecular disturbance from point to point zs the transmission of excitation. As we do not possess the power of molecular vision we have perforce to be contented with the vagueness of the ideas which these terms connote, complicated as they are by the concomitance of other apparently mysterious properties of living tissues. If re- sponse and its variations, however, be in truth mainly de- pendent on the molecular condition of the tissue and its upset, then, from molecular considerations alone, it must be possible to explain why, under certain conditions, the responding substance is increased in excitability, and under others depressed. It has hitherto been found impossible to determine what is the nature of the antecedent molecular

conditions to which these differences may be due: what it is that so determines the Zone, that the excitability of a tissue is made to undergo a profound change during the action of a particular stimulus or on its cessation; and what finally causes the fact that one identical stimulus, say that of tetanising shocks, will sometimes act to exalt, and at others to depress, the excitability of the same tissue. It is the caprice which has seemed to preside over these phenomena. that has forced observers upon the postulation of a hyper- physical ‘vital force. In the course of the present work, however, it has been shown that not only the simple pheno- mena of response, but all their complex variations also, are to be met with in the inorganic as in living matter, and that their explanation, therefore, must be sought for in the nature of antecedent molecular changes. As in the inorganic, the conditions of investigation are less complex than in living tissues, it follows that the study of molecular transformations and their after-effects there, is likely to throw much light upon that phenomenon of response which we have thus seen to be universal. | Taking first the response of living tissues, we find that the responsive change is of two kinds. This may be illus- trated by the following experiment, carried out on the pulvinus of Erythrina indica during the season of its greatest sensitiveness. The stimulus employed was that of a con- stant electrical current. When the upper half of the pul- vinus was made anode, response was found to take place by local expansion. This is seen in the up-record of figure 360. On the break of the anode, we observe a movement of recovery in the opposite direction. The pulvinus was next subjected to kathode-make, and we observe a_ responsive contraction. At kathode-break, however, we have a recovery by expansion.

We have thus observed two opposite re- sponsive effects, according to the different polarities of the stimulating agent—namely, expansion at the make of anode, and contraction at that of kathode. Since responsive effects must be due to molecular upset, or to new conditions of alignment, it is clear that contraction must be brought about by a one-directioned, and expansion by the opposite-directioned, change. This is evident in the present case, since the polar stimulating agents are opposite in their characters, and the opposition of their effects must correspond to this. Now it is necessary to distinguish these two responsive effects by opposite terms, which must needs be somewhat arbitrary. The contractile effect has thus been taken as the normal excitatory and negative. Having once adopted such a nomencla- ture, it is of course im- portant that it should be strictly adhered to. Thus, if contraction be the nor- mal response, then any-

thing which tends to Up-curve represents expansion and con- vexity. Down-curve represents con- traction and concavity. Continuous curve represents the action at make. Fic. 360. Polar Effects of Currents due to Localised Application on Upper Half of Pulvinus of Zryihrina indica garded as excitatory, and anything which opposes or retards it as depressing. The dotted curve shows the effect at break. Am = convexity induced at anode-make. Ad = responsive con-

cavity at anode-break. Km =induced concavity at kathode-make. Ké = expansion induced at kathode-break. The time-marks represent minutes. This word ‘depressing’ is, however, unfortunate, since by it might be indicated a permanent depreciation of the tissue, while diminution of the normal response is possible without such depreciation. Moderate rise of temperature, for example, with its expansive tendency, will lessen the contractile response without necessarily depreciating the tissue (p. 187). Revert- ing once more to the kathodic mode of stimulation, we know that a certain intensity of kathode is necessary, for the visible initiation of contractile response.’ Should the intensity employed be just short of this, there will be an

1 These kathodic and anodic effects refer to the normal moderate range of E.M.F, within which Pfliiger’s Law is applicable. incipient molecular distortion, in the same direction as that which precipitates the excitatory response, hence kat-electro- tonus should prove to be excitatory. But a moderate anode, with its incipient molecular distortion in the opposite direction, will retard the normal response, and thus appear to be depressory. I must here point out that these terms excitatory and depressing have ordinarily speaking no ab-

solute meaning, and can only acquire a definite significance when we have first fixed on that form of response which is to be regarded as normal. If, instead of contraction, we had regarded expansion as the normal response, then the effect of anode would have been regarded as excitatory, and that of kathode as depressing. We must therefore recognise that the very fact of contractile response being taken as excita- tory, entails as a consequence the designation of all agencies, such as K-tonus, which predispose the tissue to contraction, -as excitatory, or better pro-excitatory, while those which, like an-electrotonus, oppose this, must be regarded as depressory, or better anti-excitatory.

From what has been said, it will be understood that it is the direction of the molecular derangement which determines ‘the character of the response. That molecular upset, which expresses itself as excitatory contraction, we may call the K-effect, and the reversed molecular movement, expressed as expansion, the A-effect. ‘Thus, under anode, in fig. 360, the molecular distortion in one direction induces the expan- sive A-effect. On the cessation of this, the rebound of recovery causes a movement in the opposite direction, which may carry the molecules back, not merely as far as the equilibrium position, but beyond this. This movement, however, is in the same direction as that induced by K-make. Hence we may understand how excitation is caused, not only by K-make, but also by strong A-break. We may also understand how it is that the excitatory effect is much

We also see, in a general way, that a particular-directioned molecular movement would have the most intense excitatory value when the molecular distortion was proceeding at a rapid rate, and not so much when a condition of permanent distortion had been attained. It is for this reason that, usually speaking, the excitatory effect is most pronounced at either kathode-made or anode-break,! and not so much during the continuation of kathodic action. To recapitulate some of the principal facts enumerated above, the term ‘excitatory’ being applied to a particular- directioned distortion or K-effect, then anything which induces an incipient molecular distortion in the same direc- tion, tending to aid the K-effect, and therefore to enhance that response, will be known as K-tonus. Anything, on the other hand, which induces an incipient distortion in the opposite direction, will oppose or retard the normal K-effect, and will, therefore, be known as inducing A-tonus.

In the examples given, the opposite K- or A-effects - observed were the outward manifestations of the aggregate molecular effects induced. And from these we inferred the opposite-directioned changes which must have been their antecedent cause. In working with inorganic substances, however, and particularly in dealing with magnetic bodies, our power of molecular scrutiny is much keener. A rod of iron, for example, is known to consist of magnetic particles, each one of which is-a true magnet, possessed of polar properties. Under ordinary circumstances these magnetic molecules are in close chains, but under the action of magnetising forces they become distorted in a directive manner. Under north-magnetising force they are distorted in one direction, and under south polar induction in the reverse. The intensity of the induced magnetisation is a measure of the degree of molecular distortion, and can be gauged by the deflection of the freely suspended needle of a magnetometer in the neighbourhood. Increasing magnetising force is thus seen to induce greater magnetometric deflections,

! It is conceivable that there should be occasions in which the final condition of distortion is not attained quickly, but slowly ; or where it is Huctuating instead of stable. Under such circumstances the excitation induced would be more or less persistent or tetanic. and on the cessation of the inducing force there is usually a molecular recovery, with a concomitant return of the magneto- metric indicator to its original position. Here, then, we have a means of recording the molecular distortions induced in a substance under a given external force. We are able also to study the relation between the acting force and the distortion induced, while it is increased or diminished in a known manner. And further, keeping the acting force the same, we are here able to study the effects of various modifying agents on the response, as recorded by the magnetometer,

In all these cases, then, we have a strict parallel to the excitatory molecular changes and their variations induced in a living tissue under stimulus. But besides this local action we have also, in the living tissue, nerves possessing the property of transmitting the state of excitation—that is to say, the molecular disturbance—to a distance ; and this trans- mission is modified appropriately by the various modifica- tions which may be induced in the conducting nerve. Simi- larly I shall be able to show that, in an iron wire, excitatory magnetic disturbance is propagated to a distance; this con- duction likewise being modifiable by the molecular changes induced in the conducting wire.

Thus, in those particular cases where molecular scrutiny is possible, we are enabled to visualise with considerable accuracy those molecular events on which excitation and its transmission depend. Afterwards, discarding this illustrative class of magnetic substances, I shall refer to other methods, by which the responsive manifestations of ordinary substances under stimulus, and the modifications of these responses under various conditions, will be recorded. From so compre- hensive a study we shall find that whatever be the mode ot record, and whatever the experimental substance employed, the fundamental reaction, and its variations under particular conditions, are curiously similar. It will then be realised that the response of living tissues is not alone of its own kind, but falls under a wide generalisation,

But before proceeding further with the magnetic responses, we must call to mind two different responsive manifestations of living tissues. We have observed these under the polar action of electric currents, one being the K- and the other the A-effect. Similarly in magnetic substances also, under the action of the magnetising forces, we observe two different effects brought about by opposite polar changes. One of these is the result of north and the other of south polar in- duction ; and of these, for the sake of convenience, we shall fix our attention on the effect induced by the north pole as the normal negative or K-effect.

The fundamental molecular change induced may here, as in the case of living tissues, be recorded in various ways. In the present case, of the response of magnetic substances under magnetic stimulation, the methods of record may be classified as mechanical, magnetometric, and electro-motive. Joule discovered that a rod of soft iron undergoes a change of length on magnetisation. Though this variation is very small, I find it comparatively easy to demonstrate and record the responsive change concerned by means of the following device. One end of the iron rod is fixed, and the free end, carrying a wooden disc, rests on a tambour covered with stretched indiarubber. The tambour chamber is closed except at the point where a capillary tubing of glass enters it. This tube contains a short index. On now suddenly inducing magnetisation by a magnetising coil, the rod under- goes instantaneous elongation, and the resulting expulsion of air from the tambour causes a corresponding movement of the index outwards. Cessation of the magnetising current is attended by immediate recovery. It need only be men- tioned here that by making the diameter of the tambour sufficiently large, and that of the capillary tube sufficiently small, and by optically magnifying the movement of the index, it is easy to obtain for this mode of experiment a very high degree of sensitiveness. 5

It is much easier, however, to record responsive molecular changes by the usual magnetometric, or by the induction or electro-motive method. According to the former of these, the magnetising coil, C, is placed broadside on, in reference B, balancing coil; A, ammeter; -R, Magnetic Responses rheostat ; K, key actuated by metro- , of Iron Fic. 363. Photographic Record of Periodic Groupings in Mag- netic Responses the other side, and so adjusted as to nullify any disturbance of the needle by the magnetising coil. The experi- mental rod of iron is then introduced inside C, and the responsive molecular action induced by the exciting current is recorded in the usual manner by the deflected spot of light from the mag- netometer, M, thrown on a revolving drum. The intensity of the exciting current, measured by the ammeter, 4, is capable of adjustment by means of the rheostat, R. The duration of appli- cation of the exciting current is deter-

mined by a metronome, and thus kept uniform in successive experiments. In fig. 362 is seen a series of records obtained in this manner, employing stimulation of moderate intensity. In fig. 363 is seen a curious instance of periodic groupings in magnetic responses, similar to those obtained in living tissues. In the next figure (fig. 364) is shown the effect of strong stimulation, which gives rise to responses, not only of greater amplitude, but also of prolonged recovery. Under the strong stimulation here employed, owing to persistent molecular strain, the recovery did not become complete. This is analogous to the contracture in strongly excited -muscle. Such persistent strain may be removed by miole- cular vibration, the hastened recovery in the present record

4 being the result of a tap. Magnetic stimuli, individually ineffective, become effective by repetition. In fig, 365 is Fic. 364. Photographic Record or Response and Recovery of Steel under Moderate and Strong Mag- netic Stimulus recovery under moderate stimulus. FIG. 365. spare sie ay Record In the next two, stronger stimulus sabes: neffective Stimulus induces response of greater ampli- made Effective by Repetition tude and incomplete recovery. Molecular vibration by tap, at point marked by down-arrow |, hastens recovery.

Asingle brief magnetic stimulation induced little or no effect, but when rapidly repeated thirty times it became effective. seen a record of this. Tetanisation also induces the maxi- mum effect of fusion—as will be seen in the following chapter. Tetanisation, again, induces interesting after-effects in mag- netic responses, precisely the same as those seen in living tissues. Under certain conditions, moreover, to be fully described later, tetanisation, as we shall see, enhances the subsequent responses, while under. other conditions, by in- ducing fatigue, it brings about their depression.

the mechanical and magnetometric methods of studying response in magnetic substances, there is also a third .means available, in the Induction or Electro-motive Method, to be fully described at the end of the present chapter. I have now explained how the extent of molecular distortion induced in a magnetic substance by an external force can be gauged or measured by magnetometric or electric indications. For the detection of similar changes, however, in matter which is not pronouncedly magnetic, it is necessary to devise a method of record of more universal application. Such a method we have, as already said, in the record by resistivity-variation. It is here desirable, however, to give. a more detailed account of this and the principle involved. | |

Our object being the detection of the molecular changes induced by stimulus, let us briefly consider certain well- known cases of molecular transformation induced by various stimulating agencies. Thus, when sulphur is subjected for a certain length of time to the action: of light, there is no visible sign of any change. Its solubility in carbon disulphide, however, has been altered, and we can dis- criminate-the portions acted upon from those unacted, by means of this ‘developing’ solution. But such discrimina- tion is only possible when the molecular or allotropic modification has gone so far as to be somewhat stable—that is to say, when the after-effect of stimulus is persistent. The development of any after-effect would have been impossible had the substance in the meanwhile exhibited self-recovery. Between the original condition A, again, and the terminal modification D, the substance must have passed through many gradations of condition, of a more or less impermanent stability. This case is analogous to that of a piece of iron under the action of magnetising forces, with their consequent molecular modifications. When the acting force is moderate, and the specimen has the power of self- recovery, the induced molecular distortion—that is to say, the induced ‘magnetisation—is fugitive, and there is no after-

effect on the cessation of the force. But, under intense magnetisation, the molecular transformation is more or less persistent, and we observe an after-effect in the induced permanent magnetisation. To revert here to the illustration of sulphur, it is only because the persistent terminal change is the most easily distinguishable that we single it out for the name of ‘allotropic change. As a matter of fact we see that this is but the climax of a series of changes, and so incomplete a view has been made current by the fact that we had no means of recording the intermediate changes while they were in progress.

The next question is as to the possibility of making such records of molecular transformations, or of induced varia- tions in the state of molecular aggregation, while they are taking place. This may be accomplished, as I shall show, by the concomitant variation of electrical conductivity. It is to be borne in mind that the state of molecular aggrega- - tion plays an important part in determining the conductivity of a substance, and as an example we may take the case of carbon, which exhibits wide differences of conductivity in its two allotropic conditions of graphite and diamond. Let us imagine a piece of carbon in an intermediate or neutral state between these two. We-may suppose that an external force distorts it to a small extent towards the more con- ducting state of graphite. This distortion would be attended by an increase of conductivity, from which latter the extent of molecular distortion or upset involved might be inferred. Now, during the distortion from the equilibrium position, a force of restitution will tend to restore the carbon to its original neutral condition. If the’ distortion does not proceed beyond the elastic limit, then, on the cessation of the external stimulus, it will recover its original state, and this will be evidenced by the restoration of its original con- ductivity. But if the distortion be of a sub-permanent or permanent type, the recovery will be very much protracted, or will not take place at all. Such more or less permanent distortion, known as allotropic transformation due to stimulus

of light, is seen in the production of red phosphorus from the yellow variety, and the insoluble from the soluble variety of sulphur. It will thus be seen that the conductive aspect of a given substance is not definite, but variable, the conductivity being dependent on the particular molecular condition of the sub- stance. This peculiarity may be represented in the accom- panying model (fig. 366), if we give the cylinder representing the sensitive molecule three main-conducting aspects A B C. The non-conducting aspect is represented by c. With the sensitive substance in this particular condition, inter- posed in the electric circuit, the current in the galvano- meter would be zero. A is the semi-conducting aspect of the substance, under which we may imagine the corresponding deflection of the galvanometer to be 50. B is the highly conducting aspect, the corresponding galvanometer reading being