Comparative Electro-Physiology: A Physico-Physiological Study

face of latter. The natural current, N, gradual depression. In is in both from the less to the more ex- citable. In both excitatory current, E, order, then, to observe the is in opposite direction, z.e. from the effect of increase or de- more to the less excitable. In Musa ae increase of internal energy (+ }) in- Crease O internal energy duces a positive; and diminution of on the existing current of internal energy (— *) a negative, varia- tion of the natural current. rest, we have only to sub- ject the specimen to gradual thermal ascent or descent, and record the consequent variation of current.

The specimen of Zusa is placed in a chamber and two diametrically opposite contacts are made, with the internal and external surfaces, and led off to the galvanometer. To take first the effect of cooling: a stream of ice-cold water is sent through a hollow tube in the chamber: this gradually lowers the temperature, say from 30° C. to 27° C. It will be seen from left-hand curve of fig. 84 that this has the effect of diminishing the natural current of rest in the tissue, as represented by the dotted arrow |}. When the chamber is

allowed to’ return to the temperature of the room, this diminution of current is annulled. To study the effect, on the other hand, of a rising tempera- ture, the chamber is gradually heated, by means of the electric heating-coil already described. In thus raising the temperature, it is found (fig. 84, right-hand curve) that the natural resting-current undergoes an increase. On cooling again to the original = temperature, this in- crease is annulled. That these effects are due to induced elec- tro-motive variations, and not to any changes of resistance, is demonstrated from the fact that the effect described takes place even when the original E. M. F. is exactly balanced by a poten-

tiometer. Fic. 84. Effect ot Variation of Temperature It ‘all on Natural Current, {, which in Petiole of was specially Musa flows from Convex to Concave Side stated that these ob- Effect of cooling from 30° C. to 27° C., seen servations with regard on left, induces negative variation of natural current. Restoration to original value on tothe effect of varying return to surrounding temperature. Warm- t | ing induces positive variation (see record to emperatures apply right). In this and subsequent figures in only to steady varia- the present chapter { indicates the direction of the natural current of rest.

have seen that a steady rise brings about an increase of the existing current. But since sudden variation of tempera- ture acts as a stimulus, we shall, in the preliminary stage, obtain an excitatory reaction, which will cause a transient diminution of the current of rest. This will be followed, when the rise of temperature is steady, by am increase of the current of rest. I give here (fig. 85) a photographic record of these contrasted effects. In the first part of the curve we observe a sudden movement of the record upwards corresponding to the sudden rise of temperature. This is so great as to carry the curve out of the photographic field. We have here, then, a sudden excitatory diminution of the natural current. In the next stage, while the temperature is steadily ascending, we find a reversal of the curve, and the natural current is enhanced above. the normal. On now allowing the chamber to cool down to the original temperature of the room, the natural current was found to return more or less to its normal value.

We shall next study the effect of chemical agents on the natural current. The mode of procedure is to apply the given agent on both the contacts at the same time. If Fic. 85. Photographic Record showing effect of Sudden, followed by steady Rise of Tem- perature on Natural Cur- rent, ¥, in A/usa the substance be liquid, it can be applied by a pipette. If it be gaseous, the specimen is placed in a chamber through which the gas or vapour is allowed to stream.

' During sudden variation of temperature an excitatory negative variation of natural current: takes place, as shown by first up curve; when rise of - temperature becomes steady there is a positive variation, as shown by the down curve ; on re- turn to surrounding tem- perature, the normal cur- rent is restored to its original value. In observing the effects of various agents we obtain results which are at first sight very perplexing. For example, certain substances will be found to induce a diminution of the natural current, and others an increase. The effect, moreover, is found to be modi- fied by the strength of the dose. Thus an agent which, in a given strength, will cause a diminution of the natural current, may often be found to cause an increase, when sufficiently diluted. This inquiry is of great importance, since it is directly connected with many equally obscure problems in medical practice, where the effect of a drug

Much light appears to be thrown on this subject, when we consider the electrical reactions of the chemical agents as due to their physiological action. If a drop of hydrochloric acid be applied to the pulvinus of J7/zmosa, the leaf falls, showing that the more excitable side has undergone a greater excitatory contraction. We have also seen that when a drop of this acid is applied on any tissue in the neighbourhood of, but not directly touching, an electrical contact, it induces an excitatory galvanometric negativity. If now we apply it in solution, say, of 10 per cent. on the two diametrically opposite contacts of J/usa, we shall expect that the greater excitatory reaction induced on the concave side will give rise on that side to a relative galvanometric negativity, resulting in a negative variation of current of rest. On the application of the reagent this is found to be the case, the responsive current flowing in a direction opposite to that of rest: that is to say, it flows from the more excited concave to the less excited convex.

It is by considering chemical agents from the point of view of their physiological reaction, that we are able to explain their diversity of effects, according to the strength of the dose and the duration of application. We have seen that while a strong stimulus induces the excitatory effect of negativity, a feeble stimulus will bring about the opposite, or positivity. This abnormal positive response, however, by the continued action of moderately feeble stimulus becomes converted into normal negative. Now a chemical substance which in a certain strength acts as an efficient excitatory agent, may, when sufficiently diluted, act as a feeble stimulus, inducing a positive response. If the same agent again were applied in a slightly greater concentration, its immediate. effect might be positive, to be succeeded under continued application by the normal negative.

We might thus expect, using a strong salon of a given chemical reagent, to obtain a negative variation of the current of rest; using a dilute solution, to obtain a positive varia- tion ; and, lastly, applying a dose of intermediate strength, to discover the very interesting case in which the reagent would give rise immediately to a positive variation, and after a longer or shorter continuance of its action, to a reversed, or negative variation, of the current of rest. These inductions are found fully verified in the experiment which I am now about to describe.

Fic. 86. Action of 7 per cent. Solution Fic. 87. Effect of CO, on of Na,CO, on Natural Current of M/zsa Natural Current of AZwsa Preliminary positive variation represented Preliminary positive seen to be’ by down curve followed by reversal, succeeded by negative variation 50 seconds after application. 5 minutes after application. ; Applying a strong solution of sodium carbonate —10 per cent. or above—at the electrical contacts on Musa, the result is a negative variation of the natural current. If nowa dilute solution of I per cent. be applied on a similar specimen, we obtain a response by positive variation. And if, lastly, we use a 7 per cent. solution, we obtain, as will be seen from the record (fig. 86) the preliminary positive, succeeded, under the continued action of the agent, by reversal to the negative, variation.

We pass next to the question of the effect of gases. In fig. 87 is given a record of the action of carbonic acid on the natural current in /usa. It will be seen here that in the first stage there was an enhancement, or positive variation, of the existing current. In a later stage, however, this is followed by a reversal, the resting-current now undergoing a diminution. We have here an effect parallel to that of the intermediate dose of sodium carbonate. Vapour of alcohol also exerts an effect very similar ; that is to say, it induces a preliminary exaltation, followed by a depression of the natural

In connection with this subject, of the changes induced in the natural electro-motive difference between the two surfaces, by the action of a chemical reagent, it is well to distinguish between the effects of two different factors: namely, the electrical variation caused by the chemical sub- stance as such, and that brought about by the excitatory reaction. Let us suppose both the electrical contacts to be made on iso-electrical surfaces, with normal saline solution; there will then be no difference of potential, as between the two. But this state of things will be disturbed, by the appli- cation of another chemical solution, say acid, on either one of the two contacts. The resulting disturbance may be dis- tinguished as due to heterogeneity of chemical application. But if the same chemical agent be applied at both the contacts, no such chemical heterogeneity will ensue. If, then, any electro-motive difference be induced, it must be due primarily to some induced physiological change. The contact which has been rendered more excitable will become increas- ingly positive ; that which is more excited, on the other. hand, will become increasingly negative. That the induced electro- motive variation under such circumstances is indicative ot a variation of excitability or excitation, was seen in the fact that the same chemical agent—for example, Na,CO,— caused a positive variation when dilute, a negative when strong, and positive followed by negative under the continued action of an intermediate dose. This conclusion—that the variation of the existing current, by the simultaneous application at the two contacts of the same chemical reagent, is due

to a physiological reaction, the positive variation being a sign of relatively increased, and the negative of decreased, excitability—will be verified by an independent mode of in- quiry, to be described in the following chapter. | It follows from the experimental demonstration which has just been given that the phenomena of the natural current and its variations may be summarised in general as follows : words, the more excitable is galvanometrically positive to the less excitable.

2. Increase of internal energy induces an increase or. positive variation of the existing current ; and diminution of internal energy induces a negative variation. 3. External stimulus induces a negative variation of the true or natural current of rest. ditions have now been studied. We shall next proceed to trace out those conditions under which abnormal results may occur. Excessive cooling, by diminishing internal energy, may thus reverse the normal current, which reversal may become more or less persistent. It has been shown, moreover, that in an anisotropic organ, external stimulus gives rise to a current opposite in direction to the natural current. . By this excita- tory reaction the more excitable side, hitherto positive, is rendered negative, and if the excitatory reaction be great, it may remain fora considerable period in this reversed condition of galvanometric negativity.

We have seen that under normal conditions, the direction of the natural or true current of rest is from the less to the more excitable, and that external stimulus causes a responsive current in the opposite direction, which thus constitutes a negative variation of the current of rest. This state of things we shall distinguish as the primary condition. It frequently happens, however, in consequence of previous stimulation, with its after-effect, that extremely varied effects, appearing at first very anomalous, occur, with regard to the

direction, not only of the current of rest, but also of the current of response. We shall be able. to obtain a clear understanding of these effects, on subjecting the underlying phenomena to close analysis. As a concrete example, we may take for our investigation the various effects to be observed in the pulvinus of Mzmosa. In this anisotropic organ, the directions of the resultant current of rest and the current of response are determined, as we have seen, by the differential excitability and differential excitation of the two sides of the organ. We shall fix our attention, however, for the sake of simplicity, on the changes which occur in the more effective lower half. I shall here succinctly describe the various post-primary phases in the

changing effect, culminating in the onset of fatigue from over- stimulation. In the primary condition, as we have seen, the lower half of the pulvinus is positive to the upper, the direction of the resting-current being down ¥. On stimula- tion, the lower half becomes negative and. the response current is up t. Response thus takes place by a negative variation of the resting-current. We may now suppose the pulvinus to be in a state of slight excitation, its molecular condition at or about the B stage. This existing state of moderate excitation will annul the previous positivity, and the current of rest will now be zero. At this stage, however, as we have seen, the excit- ability of a tissue is enhanced. Hence, on stimulation, the lower half of the pulvinus will exhibit responsive negativity, and the direction of the response current will be up ft: We are, however, unable to describe this variation in terms of the current of rest, since that, as we have already seen, is zero.

A condition of still stronger excitation, bringing the tissue to the C condition, will induce galvanometric negativity of the lower half. The so-called current of rest is thus upwards t. But as the excitability of the lower half is. still relatively greater than that of the upper, it follows that external stimulus will bring about a responsive current whose direction is upwards t, This normal excitatory response, then, in this particular case, appears as a positive variation of the resting-current.

And, finally, we may imagine the pulvinus to have been strongly excited, so as to be in the condition Dor E. The resting-current will in this case be upwards ft. But the ex- citability of the lower half, owing to fatigue, has now become depressed, a condition which, as we have seen, tends to give rise to the abnormal positive response, the responsive current is upwards, this abnormal current of response will appear as a negative variation of it. All these cases are conveniently tabulated as follows :

OF REST AND THE RESPONSIVE CURRENT UNDER VARIOUS CONDITIONS. Current of rest. Current of re- | Variation of current of rest. Primary condition , | Feebly excited Moderately excited Strongly excited and | fatigued . : The various conditions mentioned may be induced accidentally in the responding organ, or may be brought about by the excitatory effect of experimental prepara- tion. I give here the records of certain experiments performed on J/zmosa, in which some of these changes were seen to occur as the result of stimulation (fig. 88). The normal natural current is seen to be from above to below, as represented by the dotted arrow. The first strong stimulus, applied at the moment represented by the thick dot, gives rise to a responsive current whose direction is from below to above, Owing to the strong intensity of the stimulation, there is here a slight indication of multiple response. As an after-effect of stimulus, we observe that the normal resting- current has undergone a reversal, the lower surface, which was formerly positive, having now become relatively negative, A second stimulus now gave rise to a response

similar to the first. But after this, owing to the greater fatigue with loss of excitability induced in the lower half of the pulvinus, the succeeding responses are seen to be reversed, the responsive current being henceforth from above to below. From the table given on the previous page, it will be seen that hardly could any standard have been devised for the study of excitatory reaction, so likely to be prolific of confusion as this, of the so called variation of the resting- current. For in the first three cases displayed, we see one identical excitatory effect, appearing now as a negative, again as doubtful, and a third time as a positive variation of the current of rest. In the fourth case, again, it is actually the abnormal response’ which appears as the normal nega- tive variation! But while these responses appear to be so various, the underlying

Fic. 88. Variation of the Transverse Natural and Responsive Currents in Pulvinus of Wzmosa Natural current } which -is normally down, reversed in consequence of strong external stimulus. The first two responses are normal, z.¢. current being from below to above. Strong stimulus is here seen to induce mul- reaction is nevertheless con- stant. The direction of the responsive current is always from the more to the less tiple responses. After the second response on account of the greater fatigue induced in the lower half of the pulvinus, the direction of the responsive current is seen to be

It has thus been shown | in the course of the present chapter that under normal conditions the current of rest flows in the tissue from the less to the more excitable; that increase of internal energy causes a positive variation of the current of rest , while its diminution gives rise to a negative variation ; that reagents which increase excitability induce a positive, and those which cause excitation a negative, variation of the resting-current ; and, finally, that external stimulus induces a negative variation of the resting-current. While these are

the normal reactions, however, under abnormal conditions, they may be reversed. Thus, excessive cooling or strong external stimulation may reverse the normal current of rest. . There are, moreover, two different conditions, those, namely, of sub-tonicity (cf p. 106) and fatigue, which may be effective in bringing about a reversal of the normal direction of the responsive current. In this way, by means of induced varia- tions of the resting-current and of the responsive current, many very varied effects become possible.

Induced variation of excitability studied by two methods: (1) direct (2) trans- mitted stimulation—Effect of chloroform—Effect of chloral— Effect of formalin —Advantage of the Method of Block over that of negative variation—Effect of KHO—Response unaffected by variation of resistance—Stimulating action of solution of sugar—Of sodium carbonate— Effect of doses—Effect of hydro- chloric acid— Di-phasic response on application of potash—Conversion of normal negative into abnormal positive response by abolition of true excitability.

IT has been said in a previous chapter that the electrical response is a true physiological response. This is demon- strated by the fact that, while a vigorous specimen gives strong electrical response of galvanometric negativity, the same specimen, when killed, whether by heat or by poison, ceases to respond. This particular electrical response is thus seen to be a concomitant of physiological efficiency. It follows that, whatever diminishes physiological activity will, parz passu, modify the amplitude of the response. But in cases in which the death of the tissue is brought about by steam or by poison, it is the last stage only, namely the abolition of response, that can be observed. It is also impor- tant, however, to be able to trace the growth of physiological changes through the concomitant modification of response. In this way it is possible not only to study the gradual onset of death, as induced by a poison, but also the action of other chemical agents, some of which might be of such a nature as to induce exaltation, others depression, and still others, like the narcotics, a temporary abolition of the electrical response.

An essential condition of this investigation is first to obtain a uniform series of responses. Having once done this, those subsequent changes in the response which are due to the appli- cation of a given reagent can be demonstrated in an unmis- takable manner. I have already explained in Chapter III. that this may be done by either of two different methods: namely, those of direct and of transmitted stimulation. Inthe first of these we employ vibrational stimulus, using the Method

Fic. 89. Photographic Record of Effect of Chloroform on Responses of Carrot Stimuli of 25° torsional vibration at intervals of one minute. of Block. In the second, the stimulus of thermal shocks is used, the excitation of the proximal contact being due to transmitted stimulation. We shall investigate the effect of chemical reagents by both these methods. And first I shall give results obtained by the employment of the Method of Block, the tissue being subject to direct stimulation. In cases where the effect of gaseous reagents, like chloroform, is to be studied, the vapour is blown into the plant-chamber (see fig. 21). In

cases of liquid reagents, they are applied on the points of contact A and B, and in their close neighbourhood. The experiment is carried out by first obtaining a series of normal responses to uniform stimuli, applied at~ regular intervals of time, say one minute, the record being taken the while on a photographic plate. Then, without interrupting this procedure, the given agent—say, vapour of chloroform— is applied, by being blown into the chamber. It will be seen from fig. 84 how rapidly chloroform induces depression of response, and how the effect grows with time. If the speci- men be subjected for a short time only to the anesthetic, the depressing action proves transient, passing off on the reintroduction of fresh air. But too strong or too pro- longed an application induces a permanent abolition of response.