Comparative Electro-Physiology: A Physico-Physiological Study

Experimental Arrangement to Exhibit the Enhancement of Excit- ability at Anode, and its Depression at Kathode, when the Acting E.M.F. is feeble positive. On now ap- plying equi-alternating shocks, the balance was Fig. 348 shows enhancement of excitability at anode; Fig. 349, the depression of excitability at kathode. ing current. Outside thick arrow, direction of excitatory current. Note that in both thereis a so-called polarisation-decrement. found to have been dis- turbed, and the re- sponsive. current to be in the opposite direction, namely, EGE’, as shown by the thick arrow; E’ now undergoing an excitatory negative variation. This shows that the ex- citability of E’ has become enhanced by being made anode. E’ was next made kathode, in consequence of which the permanent current in the galvanometer was now in the direction of EGE’ (fig. 349). E’ is now the kathode, E

in relation to it being anode. On excitation the responsive current was in the opposite direction to the permanent current, in consequence of the induced depression of the kathode E’ or the induced enhancement of excitability at the relative anode E. In fig. 350 are given the records of these effects. Two different experiments were carried out, on two different specimens of plant nerve, whose records are given in a and 4, fig. 350. In each of these we observe, first,

Fic. 350. Photographic Records of Response, illustrating the Enhance- ment of Excitability at Anode, and Depression at Kathode, under Feeble Acting E.M.F. in two Specimens of Nerve of Fern a and 6 Before application of polarising current there was no resultant response in either case. When E’ was made anode, there was an up-response, indicating enhanced excitability of that point.. The dotted arrow ¥ seen below shows the direction of polarising current. The responsive current is then opposite in direction to the polarising current. When E’ is made kathode the resultant response is down, showing depression of the excitability of the point. The responsive current is here also opposite in direction to the polarising current.

the enhanced excitability due to E’ being made anode, which gives rise to up-responses, opposite in direction to the permanent current, shown by the dotted arrow below. The second pair of responses in each case shows the depression of excitability at the kathodic point E’, which is tantamount to enhancement of excitability at the relative anode E. An inspection of figs. 348 and 349 will show that the responsive current is always in a direction opposite to that of the existing polarising current, thus constituting the so-called polarisation

decrement. But we shall presently find that the direction of the responsive current is the only constant factor here, de- termined as this is by the relative excitabilities of the. two electrodes. An identical variation of excitability may, as I shall show, appear under different circumstances, either as a polarisation-increment or as a decrement. I have obtained results precisely like the foregoing, with the sciatic nerve of frog. It should be mentioned here that such effects are obtained without much difficulty in the first stages of polarisation. But, if this be prolonged, there is a certain liability to reversal.

From the experiments which have been described on variations of excitability by the polar action of currents, we arrive at the following law: A feeble E.M.F. induces modifications in the excitability of a tissue: the anode enhances and kathode depresses excitability. This result is startling, contravening, as it does, Pfliiger’s Law. A factor that had not been taken into account was the range of E.M.F., within which this law might be applicable. In the present case, the acting E.M.F. is relatively feeble, and we shall see later that Pfliiger’s Law does not apply above or below a certain medium range.

Having thus obtained the isolated effects of electric currents on conductivity and excitability respectively, I next took up those more complex cases in which both effects were present in various combinations. This problem was attacked by means of the Conductivity Balance. In this experiment, carried out on the petiole of fern, the led-off points E and E’ were at a distance of 6 cm. from each other. The distance of each of the polarising electrodes A and K outside the led-off circuit E’ and E was 2 cm. (figs. 351 and 352). The thermal stimulator S was so adjusted before the passage of the current that the excitations at E’ and E were exactly equal, as seen in the balanced horizontal record n fig. 353a. It should be mentioned here thatthe galvano- meter connections were so arranged that an _ increased excitability of the left-hand contact E’, would be shown by

Variation of Conductivity and Excitability by Polarising Current employed to induce polarisation, the anode being in the first Fic. 353. Photographic Record of Response under the Arrangements given in Figs. 351, 352 in Nerve of Fern 4, Resultant response downwards when polar- ising current is from left to right, as shown by arrow —. This shows excitability of FE’ and conductivity in direction SE’ to be relatively enhanced. c, Resultant response upwards when polarising current is from right to left <. This shows excitability of E and conductivity in direction SE to be relatively enhanced.

at E’ by the proximity of the anode, that of E being depressed by the proximity of kathode. Of the two waves of ex- citation, moreover, which proceed in opposite di- rections from the stimu- lator S, that towards E’ is moving electrically uphill, or towards the anode, and owing to increased conductivity in that direction the excitation is better con- ducted than in the case of the second wave, which is _ proceeding electrically downhill to- wards the kathode at E. It must also be

remembered that not only is the intensity of excitation which reaches E’ greater than that which reaches E, but also that the point E’ is itself rendered more excitable by the contiguity of the anode, while E is depressed by that of the kathode. Hence, by the concordant action, at each end of the balance, of conductivity and excitability changes, and owing to the opposite nature of these changes at opposite ends, the original balance is disturbed, and we obtain resultant down responses, showing the greater excitation and galvanometric negativity caused at E’ than at E, when anode is to the left and kathode to the right. This is exhibited in the first pair of down responses in figure 353 4. When, however, the polarisation current is reversed (fig. 352), the excitation at the right-hand side, E being now near the anode, is relatively the greater, and we find the resultant responses to be upwards, as seen in the third record in fig. 353. To go back to the question of the relative directions of electro- tonic and responsive currents, we find in that case, when the anode is to the left, that E’ is galvanometrically positive, while the excitatory change makes it galvanometrically negative. This means that the excitatory response takes place by the so-called polarisation decrement. When the anode again is to the right, the galvanometrically positive E tends by excitation to become galvanometrically negative. This will be clearly understood from the arrows which accompany the diagram, in figs. 351, 352. The inner and thin arrows represent the direction of the polarising current, and the thick outer arrows the responsive current. These results are tantamount to an example of the so-called polarisation- decrement. In order to show, however, that the. same excitatory reaction might appear as a polarisation-increment, I shall describe another experiment.

The experimental tissue is here the isolated nerve of fern, and the method employed is again that of the Conductivity Balance. In this case, however, it will be noticed (figs. 354, 355), that the galvanometer is included in series with the polarising E.M.F., instead of being placed as a shunt, as in the lastcase. The stimulator was first adjusted at halance. The left electrode was now made kathode, the right being anode, the E.M.F. employed being °2 volt (fig. 354). On account

of the increased excitability of A at the anode, and also of the greater intensity of excitation conducted towards it, the balance was disturbed, and the resultant response ‘took place by the enhanced galvanometric negativity of that point. The responsive current thus constituted an increment of the polarisation-current, as seen from the arrows; of which the thin inner represents the polarisation and the thick outer the responsive current. On now reversing the current again; the right-hand end being made anode and more excitable, the resultant response was found to take place by the enhanced negativity of that point, thus again constituting a polarisation increment (fig. 355). I give here two different

Fic. 354. T'IG. 355. Figs. 354, 355. - Experimental Arrangements for Showing so-called Polarisation-increment by the Joint Effect of Increased Excitability at Anode and Enhanced Conduction of Excitation electrically Uphill sets of photographic records, obtained with the nerves of fern and frog respectively. Balance was first obtained at the beginning of the record, but on the passage of the polarisation current, this balance was found to be disturbed. When the right end of the balance was made anode, the resultant response on excitation was up, demonstrating the enhanced excitability of the anodic point. When the right- hand end, however, was made kathode, the balance was upset in the opposite direction, that is to say, down, showing that the left-hand anodic point was now the more excitable. Fig. 356 gives a record of these responses as obtained from the nerve of fern, and fig. 357 from the nerve of frog. The responsive currents in these cases, it should be noted, are in the same direction as the polarising current.

On referring to the experiments on polarisation increment and decrement which have just been described it will be noticed that the excitatory reaction is the same in both cases, taking place by the enhanced galvanometric negativity of the more excitable anodic point. The seeming difference in the electrotonic variation in the two cases lies simply in the fact of the different dispositions of the galvanometer. This occupied, in the first case, the position of a shunt in the polarisation-circuit, while in the second it was placed in series.

From the investigations which have been described, we shall now find ourselves in a position to explain the various Fic. 356. Photographic Record of Responses in Nerve of Fern, under Anodic and Kathodic Action, as described in Figs. 354 and 355. The upsetting of the balance is upwards, when the right-hand end of the balance is made anode, proving the enhanced excitability thus induced. Resultant response downwards when the right-hand end of the balance is made kathode.

Fic. 357. Photographic Record of Similar Effects in Nerve of Frog. experiments of Hermann and Bernstein, and to show that these, although apparently conflicting, are really mutually consistent. First, then, to take Hermann’s experiment, and referring back to figs. 341 and 342, in which the galvanometer is placed in series in the polarisation-circuit, we find this to be an instance in which we have to deal almost exclusively with the effect of anode and kathode on excitability. Simultaneous excitation of the anodic and kathodic points by alternating induction currents, induces greater excitation, and consequent enhanced negativity of A. The responsive

current, being thus concordant with the electrotonic current, causes an increase of it, the so-called polarisation-increment. In Bernstein’s experiment on polarisation-decrement, we are confronted with a question of greater complexity, for here we have to deal with changes of conductivity and excitability at the same time. We shall first take the -case (fig. 339) in which one electrode of the led-off circuit E is under kat-electrotonus. EE’ is therefore relatively anodal, and consequently more excitable. The excitation from the stimulator S which reaches E’ is in this case impeded in reaching E by the fact that it has to travel electrically downhill—that is, from the anodal E’ to kathodal E. Thus, owing to the greater excitation which reaches E’, and owing also to the greater excitability induced in it by the fact that it is relatively anode, excitation induces a relatively greater galvanometric negativity of that point. The thick arrow in the figure indicates the excitatory current, which is opposite in direction to the polarisation current, which latter is indicated by the thin arrow. In the second case, when the polarisation current is reversed (fig. 340), E is anodal, and _ therefore relatively more excitable, and E’ kathodal, and there- fore less excitable. Unlike the last case, the excitation from s, in order to reach FE, has now to travel electrically uphill from the kathodal to the anodal points. The excitation of E therefore is in this case not impeded. Hence greater excit- ability of E makes that point, on stimulation, galvanometrically negative, and the responsive current, represented by a thick arrow, brings about a diminution of the polarisation-current. It has thus been shown, in the course of the present chapter, that the same electrotonic effects are exhibited in the case of the plant, as in that of animal, nerves.

It has been shown that various apparently anomalous results may be brought about by simple combinations of two different factors. Thus, the so-called polarisation increment and decrement are not mutually conflicting. They are, on the contrary, due to the distinct and definite effects induced by electrotonus on conductivity and excitability respectively, As regards conductivity, it has been shown that excitation travels best in the direction electrically uphill—that is to say, from a place of low to one of high electric potential. In consequence of this fact a moderate excitation becomes enhanced when travelling from the kathodic to the anodic region. Conductivity is depressed, on the other hand, from anode to kathode. An excitatory impulse is thus retarded in travelling electrically down-hill. For these reasons, a normal negative excitatory effect may, during transmission, undergo either diminution of intensity, or actual reversal to positive.

With reference, again, to electrotonic variations of excita- bility, we have seen that under feeble E.M.F. it is the anode that exalts, and the kathode that depresses. This conclusion. is obviously opposed to the generalisation known as Pfliiger’s Law, the extent of the applicability of which will be discussed in detail in the following chapter. Reversal of Pfliiger’s Law under high E.M.F.—Similar reversals under feeble E.M.F.—Investigation by responsive sensation—Experiments on _ living wounds—Under moderate E. M.F., intensity of sensation enhanced at kathode, and depressed at anode—Under feeble E.M.F., sensation intensified at anode and depressed at kathode—Application of electrical currents in medical practice.

IN studying polar variations of excitability in nerves, in the last chapter, we found that, during the passage of the current, it was the anode which enhanced excitability and the kathode which induced depression. Now this conclusion, as will be remembered, is directly opposed to what is known as Pfliigers Law, the universal applicability of which has hitherto been regarded as beyond dispute. Pfliiger’s Law lays it down that the kathode excites at make, and the anode at break; and that, moreover, during the passage of a constant current, excitability is raised at or near the kathode, and depressed at or near the anode. We are next, then, led to inquire: Under what conditions is this law applicable, and when does it fail to hold good? Now, as regards the effects at make and break, I have shown elsewhere, in the course of experiments on plants, that these are not determined by anode and kathode alone, but also by the intensity of the acting electro-motive force. Thus, in the case of the sensitive Biophytum, in a given experiment it was found that, using the moderately strong E.M.F. of 24 volts, the excitatory wave at make was found to be initiated at kathode, and to travel in both directions, causing depression of nine pairs of leaflets. The forward half of this wave of excitation, stopped only at

one pair of leaflets before the anode. There was no action at the anode itself at make. After a suitable interval, during which the leaflets re-erected themselves, the current was interrupted. There was now no action near the kathode at break; but excitation was induced at the anode, as was shown by the fall of three pairs of leaflets in its vicinity (fig. 358), The experiment was now repeated by reversing the direction of the current. The poles being thus reversed, eight pairs of leaflets fell at the new kathode, in and out. There was no effect, however, at the new anode at make. But at break, excitatory reaction was _ ini- tiated at the anode, and none at the kathode.

These are the normal effects, falling under Pfliiger’s Law, which holds good within a certain medium range of E.M.F. But when the E.M.F. is much higher, I find that these normal effects become Fic. 358. Make-kathode and Break- reversed. Thus, employing anode Effects in Bzophytum EMF. of lts-j Upper figure shows effect at make, an i.M.I'. Of 220 volts, it was excitation being produced at found that excitation took kathode. Lower figure shows effect at break, excitation being place at the anode at make, now produced at anode.

the leaflets passing slowly thence towards the kathode. At break, excitatory action was initiated at the kathode, the wave of excitation then passing towards the anode. I thus found, by the employment of a very high E.M.F., that the normal polar effects were completely reversed. Intermediate between these two extremes of normal and reversed action, I obtained a transitional phase, in which both anode and kathode were seen to excite at make. At break also there was here occasional excitation, at either anode or kathode. Similar reversals and transitional effects have also been noticed, in the case of certain protozoa by Kiihne and

and by the kathode at break. Actinospherium, again, shows excitation on make, at both anode and kathode, and on break at the kathode only. Having thus demonstrated the fact that an excessively strong E.M.F. induces a reversal of the normal polar effects, it may not appear improbable that there should be a similar reversal of these effects when the intensity of E.M.F. is varied in the opposite direction, that is to say, when it is | very weak. I have already drawn attention, in many places, to the importance of this factor of intensity in determining the excitatory effect of a stimulating agent. A chemical reagent, for instance, when administered in moderate or very dilute doses, will induce one effect, say that of exaltation, and, in greater quantities, the very opposite, or depression. A poisonous reagent, again, which usually induces depression, will, if given in sufficiently minute quantities, have the effect of exaltation. These reversals, under varying intensities of the external agent, are noticeable again in different physico- chemical phenomena. Thus it is well known that in the formation of the photographic image, while a moderate _ intensity of light gives us the normal ‘negative,’ a stronger intensity will produce a ‘ positive,’ and a still more intense light, bring about a re-reversal. We may thus have a series of recurrent reversals.

- Returning, then, to the question of polar action on excitability, we find that the typical results of Pfliiger with nerve and muscle preparations, were obtained when using a moderately strong E.M.F. In this, which is sometimes distinguished as the third stage, excitatory contraction of the muscle is induced, only on the closure of the descending current, or opening of the ascending. In the former case, the kathode is nearest the muscle, and as there is no inter- mediate block the excitation is clearly due to the make-action of the kathode. In the second case, similarly, the break of the anode, which is now near the muscle, causes excitation. With very weak E.M.F., however—that is to say, in his first stage—Pfliiger found that excitation took place by the make

of both ascending and descending currents, but not at the break of either. Extending the clear inference of the previous case to cover this, it was supposed that here, too, the kathode—at one time near to, and at another far from, the responding muscle—excited at make. But this is not so conclusive, since the anode might equally well be regarded here as causing the excitation at make. Indeed this supposition that a very weak anode might cause excitation at make derives some support from Heidenhain’s experi- ments. For, using a weak E.M.F., he found make-excitation to occur in the first stage only, when the current was ascending—that is to say, when the anode was near the responding muscle. This result would tend to show that there was a possibility of the reversal of normal polar effects when thé acting E.M.F. was weak. With regard to this particular effect of minimal currents, there are considerable differences of opinion. The obtaining of such an effect is probably only possible when the nerve-muscle preparation is in an exceptionally favourable condition of excitability, a state of things not always possible to secure in the isolated specimen. It therefore occurred to me that the effect of a feeble anode in enhancing excitability might be demon- strated conclusively in the case of the vigorous intact animal. With this consideration in view, I carried out a number of experiments on certain of my students and myself.

If we make a slight wound, say one square cm. in area, on the back of the hand, and apply a solution of salt, which is not too strong, a constant sensation is induced which cannot be called painful, but may best be described as smarting or irritating. If now we apply one non-polarisable electrode on this wound, and the other on a distant and indifferent point, then, on applying an E.M.F. to the circuit, charac- teristic variations of sensation will be induced, depending on whether the wound-spot is made anode or kathode (fig. 359). Employing an E.M.F. of 2 volts, it will be found that when the spot is made kathode, the sensation, which was previously one of mere general irritation, becomes

intensely painful. This is because the kathode, at make and during its continuation, induces an enhancement of the excit- ability of the wound-spot. On the cessation of the current, the painful sensation disappears, and the normal smarting is restored. The wound-spot was next made anode, with Fic. 359. Effect of Anode and Kathode on ROSES Sensation in Human Hand By means of reversing key, R, E in connection with the esha: -spot may be made anode, and E' kathode, and wice versa. By alternately pressing the keys, K’ and kK, feeble or moderately strong E.M.F. may be em-

ployed. the same E.M.F. as before. The sensation now experienced was one of soothing, the sense of smarting irritation having disappeared. On the stoppage of this current the original irritation was again restored. In these experiments we have typical instances of the kathode inducing increase of excitability, and the anode depressing it, during the continuation of the current, a verification, by means of responsive sensations, of Pfliiger’s Law. Having thus, with moderate E.M.F. obtained the excitatory effect at kathode, and depressing effect at the anode, by means of the contrasted sensations of intense irritation and soothing, I was next desirous of seeing whether, with low E.M.F., these effects would be reversed. I therefore undertook investigations on a dozen different individuals, to determine the effect of anode and kathode, as the E.M.F. was gradually increased from *3 to 2 volts. It should be mentioned here that the subjects of the experiments were totally ignorant of the object of the investigations, and were simply asked to describe their sensations at different points. Their ages varied from eighteen to twenty-five. As the critical point may undergo some variation with the season, it may be worth while also to mention that the experiments were carried out in summer, in the month of August. The following case may be taken as typical :

PoLAR EFFECTS OF E.M.F. oF VARIOUS INTENSITIES ON RESPONSIVE Acting E.M.F. | Effect on wound-spot when kathode Effect on wound-spot when anode *3 volt Slightly soothing Marked increase of irritation So _ Slightly soothing Marked increase of irritation os eee Increase of irritation Indifferent ES 155 Increase of irritation Slightly soothing 2°0 volts Painful Soothing It will thus be seen that the kathode, which, at the moderately intense E.M.F. of 2 volts, induced a painful sensation, owing to the increase of excitability, induced the very opposite effect of depressing excitability at the low E.M.F. of -3 volt. Precisely the reverse, moreover, was the case with the anode. Here, with ‘3 volt, excitability was found to be enhanced, causing increase of irritation, while, with the moderately strong E.M.F. of 2 volts, it induced the opposite effect of soothing, by depression of excitability.