Principles of General Physiology

The hardness of a muscle is proposed by Noyons and von Uexkiill (1911), as a test of the tonic activity of the catch mechanism. In the leech, the same length of animal may in one case be under a tension of 10 g., in another of 70 g., and, to the eye, they have much the same appearance. Tested by the apparatus of the above investigators, the greater hardness of the latter is made apparent. Although it seems established that certain muscles are able to hold up, by means of the "catch" mechanism, a weight for a considerable time without appreciable consumption of energy, the work of Cohnheim (1912, 3) on Xi/titiicu/tt*, and of Cohnheim and von Uexkiill on the leech (1912), showed that, when loaded, the energy consumption is greater in these animals than when unloaded. But it is plain that it is difficult to be certain that there is no reflex effect on other muscles or organs, on account of the abnormal conditions present.

An appropriate form of apparatus for the investigation of the phenomena of tonus, especially in the snail, is described by Jordan (1908, 1912). Of course, the comparison of the mechanism in question to that of a catch or ratchet is only intended to assist the reader in grasping the mechanical conditions present, which are similar in both cases. As to the actual process itself, hypothetical suggestions only can be made in the present state of knowledge. The state of tension into which a skeletal muscle of the vertebrate is put by stimulation, passes off automatically when the stimulus is removed. Whatever may be the cause of this increased tension, whether the setting free of some

substance which increases surface energy or osmotic energy, it disappears again spontaneously, under the usual conditions. The permanent tonic state of the smooth muscle, which we have been discussing, might be explained by supposing that the internal changes in the muscle cell, which result in the increase of tension, are prevented from disappearing. The mechanism which is responsible for the bringing about of this temporary irreversibility of the contractile process, may be put into action, or inhibited, by the intervention of special nerve fibres. The state of tension into which excitation puts the muscle thus remains until the external inhibitory influence comes into play and sets going the opposite process associated with relaxation, in which the products of the contractile process disappear.

We have, in fact, indications of something of this sort in the "contracture," associated with fatigue, in the skeletal muscle, as well as in the action of veratriiie (page 417) and of certain electrolytes (Mines, 1912). Moreover, we shall see presently that the tonic contraction of decerebrate rigidity presents some peculiarities of this nature, when compared with ordinary reflex or If we suppose the actual state of contraction of the muscle, as well as the excitatory process which precedes the contraction, to be associated with some degree of electrical negativity, and this seems to be the case, at all events, in the heart (see Figs. 172 and 173) and in the voluntary muscle under veratrine

FIG. 172. ELECTRICAL CHANGE WITHOUT CONTRACTION. — The uppermost curve in each of the three tracings is the movement of a lever connected to the auricles of the frog's heart. The middle one is the record of the string galvanometer. The lowest one, the beat of the ventricle. The iipper tracing is a normal one, the perfusion fluid containing calcium. The middle tracing shows the effect of omitting calcium. The electrical change persists, but there is no change of form of the muscle. The lowest tracing was obtained after adding strontium in amount equivalent to the calcium of the upper tracing. The beats return, as Ringer showed, but are considerably increased in duration. Note, especially in the last curve, that the electrical change begins and ends rather earlier than the mechanical one, but that the total duration is the same.

the observations of W. F. Ewald (1910) are to the point here. Examining the adductor muscle of Anodonta, he found two states of electrical negativity, one, the " twitch " current, which appears at the beginning of a reflex closing of the shell, probably the contraction of the motor muscle, and another one following this, a slow one, and apparently proceeding pari passu with the degree of tonus of the catch muscle. This latter is, according to the investigator, steady

and not of a discontinuous nature, in fact it seems like that of the mechanical state of the muscle. One would be inclined to associate it with the persistence of the state of tensile stress, which, owing to the existence of the mechanism preventing its disappearance, remains in the state to which it was brought by the stimulus. If the electrical response is due to the disappearance of the polarised state of some membrane, owing to its becoming completely permeable, it might be supposed that the mechanism consists in some method of maintaining the state of permeability.

The auricle of the tortoise, as shown by Fano (1887), undergoes slow rhythmic changes in tonus, on which the ordinary beats are superposed. Rosenzweig (1903) showed that these tonic contractions are due to the presence of non-striated muscle fibres. Fano and Fayod (1888) had shown that the vagus nerve increases these tonic changes, an action opposite to that which it exerts on the auricular muscle proper. Oinuma (1910) confirmed this result, and showed further that the sympathetic nerve inhibits the tonic changes.

The interests of these facts is that, as Gaskell points out, it seems that some extraneous muscle, which has similar relations to the vagus and sympathetic as that of the alimentary canal, must have been incited in the heart muscle during the course of evolution. Upper curve — electrogram. Lower curve — mechanical response. The tonic state into which certain skeletal muscles, most markedly the extensors of the limbs, fall after separation of the centres below the corpora quadrigemina from the higher parts of the brain, has been described above (page 417). Sherrington (1909, 3) has discovered that this condition shows several remarkable properties, which remind one in many ways of those of the smooth muscles just described, the "difference being that, in the skeletal nniM-le, the phenomena are due to the intervention of the central nervous system. These phenomena are of such a nature as to have led their discoverer to call the state " Plastic Tonus."

Suppose that we start with a limb in the rigid state, with extensors contracted, grasp the fore limb and attempt to flex it. After a certain latent time, the resistance to. movement will be felt to relax and the limb can be flexed to any point desired. The striking thing about this degree of flexion is that the limb remains fixed in the position to which it was moved. Again, suppose that the tonic rigidity has relaxed spontaneously, as usually happens, and that we place the limb in various degrees of extension, again it remains where it was placed. These phenomena are due to reflexes from the proprio-eeptors in the muscles themselves, since they disappear after section of the dorsal roots containing the afferent fibres from these receptors.

The existence of this tonic reflex from the muscle itself can be shown by stimulating the uncut nerve to it at a rate of about four to five stimuli per second. A continuous steady contraction curve is traced; whereas, if the nerve be cut and its peripheral end stimulated in the same way, a series of separated twitches is traced. Similar results can be obtained by causing reflex contractions in the normal and in the " de-afferented " muscle. The former are of a tonic nature even

when the stimuli are separated by intervals, the latter are clonic and consist of a short response to each stimulus. Since the leg is maintained in a different position, even when it is loaded, it is clear that a particular length of muscle may be in equilibrium with different loads ; in other words, the same length of fibre may have different tensions, just as we saw in the case of the involuntary muscle. Another point of interest is that the reflex contractions of the de-afferented muscle are fatigued sooner than those of the muscle in its normal state.

The mechanism must consist in each particular length of the muscle being able, in some way, to stimulate the receptors of this muscle in such a manner as to maintain the degree of contraction at this level. We must next consider certain experimental facts which show that this reflex tonic contraction is a different thing from a steady contraction of the same height, produced by the application of repeated induction shocks to the cut' nerve at a sufficient rate to give a fused curve, or from the ordinary spinal reflex described in Chapter XVI.

Inhibition of T onus. — It will be remembered that Sherrington showed that, in the case of spinal reflexes, by appropriate relative strength of stimuli applied to different nerves, one excitatory, the other inhibitory, any degree of reflex contraction of the vasto-crureus can be obtained. Curves illustrating this fact are given in Figs. 118, 122, and 123, on pages 410-415 above, and a further one in the upper curve of Fig. 174. But, supposing that, instead of the ordinary reflex contraction, which can be reduced to any desired extent by different strengths of the stimulus to the inhibitory nerve, we take the tonic contraction of decerebrate rigidity and attempt to reduce it to different degrees by varying the strength of the stimulus of the same inhibitory nerve. It was shown by Sherrington (1909, 2, pp. 256 and 257) that no algebraical summation is possible ; any strength of stimulus which has any action at all produces a gradual fall in the height of the tonus, which fall continues until complete relaxation results, if the stimulation is continued long enough. In other words, instead of falling rapidly to a certain point and remaining there, the tonus completely disappears. The only difference between the effect of strong and weak stimuli is the rate of fall, as is seen in the lower curves of Fig. 174. One is again reminded of the removal of the "catch" in the inhibition of the adductor muscle of the scallop, although the mechanism is peripheral there, central here.

Frohlich and Meyer (1912) again, have noticed phenomena with tetanus toxin which lead them to regard the relaxation of mammalian muscle as being, in some way, directly under the control of the central nervous system. If a particular segment of the spinal cord is poisoned with this toxin, the muscles supplied by this segment enter gradually into a state of shortening. In this state, the metabolism of the muscle appears to be abnormally small ; glycogen accumulates in it. It gives no muscle sound and no vibration on the string galvanometer. If, however, the muscle is passively stretched by pulling upon it, the muscle sound is heard and the galvanometer shows the characteristic vibratory current of action of voluntary tetanus. On the view suggested above, it might be supposed that the process (production of lactic acid) which is responsible for the increase of tension has become, so to speak, permanent ; hence the state of surface tension does not disappear spontaneously, owing to the removal of the acid under the influence of oxygen, but requires some nervous influence to set the necessary mechanism into play. The phenomenon differs, however, from those of involuntary muscle in that, in the cases under discussion here, it is of central origin, as remarked in the preceding paragraph.

Metabolism. — In the experiments of Frohlich and Meyer, as given above, it was noted that the metabolism was unusually low. Now Roaf (1912) has described experiments in which he found that the carbon dioxide output and also the oxygen intake were no greater in the state of decerebrate rigidity than in a subsequent period in which the contraction was abolished by the use of curare. It should be stated that Lovatt Evans found the metabolism to be less under curare than in decerebrate rigidity. Of course, care was taken in both sets of experiments to prevent fall

1. A, Reflex contraction of vasto-crureus muscle in decapitated cat. At the rise of the signal 1, the ventral end of an inhibitory nerve (ipselateral peroneal) was stimulated. Since the muscle was free from tonus, no apparent result was obtained. At the rise of the signal C, an excitatory nerve (contrilateral peroneal) was stimulated — a certain degree of contraction. When the inhibitory stimulus was removed, there was a much greater contraction, showing that the previous condition was one of balance. Time in seconds above.

1. B, A similar experiment, with relatively greater strength of inhibitory stimulus. The grade of contraction is less than in 1, A. Note the continued steady position of the muscle in the different degrees of relaxation. •2. Vasto-crureus in decerebrate rigidity. Reflex inhibition produced by stimulation of the ipselateral peroneal nerve, with slowly repeated break induction shocks shown by signal lines SA to SB. Time in fifths of seconds by signal TA— TB.

In experiment A, the strength of the stimulus was greater (100 Kronecker units) than in B (20 Kronecker units). In both, the relaxation proceeds to the full resting length of the muscle ; but, in A, it is rapid and attained after nine shocks, while in B it is reached slowly in eighty -si v shocks of the weaker stimulus. The signal line at the foot of the figure marks the'duration of the stimulation in />'. Note that no permanent intermediate state, due to balance of degrees of excitation and inhibition, is obtained in this state of decerebrate tonus.

in the temperature of the preparation. In any case, it seems fairly certain that much less metabolism is associated with the tonic form of contraction. This result again is to be compared with the experiments of Parnas and of Bethe given above. The reader may also be reminded of the inefficiency of the sartorius muscle of the frog when maintaining a weight by stimulation of its nerve 'with induction shocks. This result led A. V. Hill (1913, 4, p. 319) to suppose that there must be a more efficient mechanism for the purpose in the normal organism. It is suggestive that Hill found, in the same series of experiments (p. 317), that the amount of heat produced per unit of tension developed, is independent of the frequency of the stimuli, provided that the latter are sufficiently rapid to cause complete fusion of twitches.

Pembrey (1903) noticed that the panniculus carnosus of the hedgehog, which keeps the animal rolled up into a ball, was in a state of tonic contraction during hibernation, a fact which adds confirmatory evidence to the view of Roaf that decerebrate rigidity is not associated with any considerable increase in metabolism. Heat Production. — I have myself made some experiments (1912, 3) on the heat production in muscles in decerebrate rigidity. Although the work is not yet complete, I found that there is a certain amount of heat produced, in magnitude varying with the degree of tonic contraction, although it is undoubtedly very much less than that produced in an artificial tetanus of a similar height.

Electrical Change. — According to Buytendyk (1912), the electrical change in decerebrate rigidity, as shown by the string galvanometer, is discontinuous ; a fact which leads him to regard it as a periodic discharge fronr nerve centres, similar to tetanus. Hofmann (1913) finds a similar oscillatory discharge in the normal tonus of the eye muscles of the rabbit. We are not compelled, however, to consider this to be the same thing as ordinary tetanus ; the putting in action or removal of the "catch" mechanism might take place in a series of discharges. Sherrington's inhibition experiments show that the relaxation is not instantaneous. The amplitude of the electrical waves is less than in ordinary reflex tetanus. But it is not possible to lay much stress on this fact, since it might be caused by the phases of contraction not being synchronous in all fibres. Buytendyk, however, points out that the oscillations in his curves are very regular, which seems to indicate synchronous state of contraction in all fibres.

Production of Creatine. — Pekelharing and van Hoogenhuyze (1910) found anexcess of creatine in invertebrate muscle in tonus, and Pekelharing (1911) found creatinine in the urine of men after prolonged voluntary tonic contraction, but not after walking. The results of Cathcart and Leathes on uric acid have been mentioned previously (page 289). Leathes and Orr (1912), further, repeated Pekelharing's experiment and found both uric acid and creatinine increased.

Relation to Labyrinth. — Ewald (1894) pointed out the important relation of the labyrinth to the maintenance of tone in the muscles generally and the loss of tone resulting from destruction of the semicircular canals. More detailed investigations were made by Magnus and De Kleijn (1912) by the use of a method devised by the latter. It was found that the tonic contraction of the limb muscles in decerebrate rigidity, especially those of the fore limbs, -was greatly influenced by changing the position of the head. Further analysis showed that there are two factors at work, reflexes from receptors in the labyrinth and reflexes from proprio-ceptors of the muscles of the neck. The former are concerned with the relation of the head to space, independently of its relation to the trunk. The latter are concerned merely with the position of the head in relation to the trunk. The labyrinth can be rendered inoperative by the injection into it of a 20 per cent, solution of cocaine, according to the method of Do Kleijn (1912). The neck effect can be excluded by making the neck immobile on the body by encasing it in plaster of Paris. It was found that the labyrinth receptors are not affected, as regards their influence on tonus, by change of position in a horizontal plane, but changes in the vertical plane have great effect on the tonus of the limbs. When the head is in such a position that the vertex is upwards and the nose at an angle of about 4o° looking downwards, extensor tonus is minimal ; with the vertex downwards, and the nose at 45° upwards, that is, on rotation of 180°, tonus is maximal. It was noticed that, along with contraction of the extensors, there was inhibition of the flexors. Moreover, in this connection it is interesting to note that Magnus and Wolf (1913) subsequently found that

strychnine does not reverse the inhibitory phase of this reflex, at all events in any possible dose. Fio. 175. ACCESSORY (SYMPATHETIC) NERVE-ENDINOS IN VOLUNTARY MUSCLE. A, From intercostal muscle of young rabbit. Magnified 1,700 times. af. Accessory nerve fibre, which is seen to be connected with the peri vascular (sympathetic) nerve plexus. This fibre ends in a special structure, independent of that of the motor fibre. »»/, Motor fibre, with branch, ending in ordinary end-plate.

B, From a section of thes uperior oblique muscle of the cat's eye. After section of the trochlearis nerve and degenerain. Degenerated motor-nerve fibres with remains of end-plate. «/, Accessory fibres intact. The hypolemmal ending of one is seen in profile. C, Knding of fine non-medullated fibres, aj, on muscle fibre of the rectus superior oculi of the cat. These endings he in a granular, nucleated protrusion of sarcoplasm. The nerve fibres themselves have nuclei here

bl, A blood vessel, upon which a fine branch of the accessorv fibre, af, is distributed. Magnified 1,800 times. Silver impregnation of sections from material fixed in formaldehyde ; sometimes treated with gold afterward-;. The neck reflexes were also found to follow definite laws, for which the original paper of Magnus and De Kleijn must be consulted. By combination of the two factors, all the complex phenomena of the decerebrate reflex tonus could be explained.

The fact that the labyrinthine reflexes are only to be obtained by changes of position in relation to gravity, and the fact that they are permanent as long as the new position lasts, indicate that they proceed from statolith organs, rather than from the semicircular canals themselves. The change of tonus, as just remarked, is a permanent one, as long as the new position of the head is maintained. In the experiments of Magnus and Wolf (1913), the preparation was so made that the changes in length of the isolated triceps or vasto-crureus could be traced on smoked paper. The above results were confirmed, and it was shown very clearly how, in this tonic state, a muscle can have different lengths under the same load.

Relation to Sympathetic Nerves. — Certain facts have been brought forward recently which appear to indicate that the tonic state of skeletal muscle may have something to do with sympathetic innervation of this kind of muscle. But caution must be exercised until further work. Boeke(1911) described accessory nerve endings in various voluntary muscles, which appear to be of sympathetic origin (see Fig. 175). In preparations A and C of Fig. 175, it will be seen that there is continuity of the fibre going to the accessory ending with the plexus around the small blood vessels. In a later paper (1913), Boeke shows that the accessory endings do not degenerate on section of the motor nerves to the eye muscles, whereas the motor endings do (see Fig. 175, B). De Boer (1913, 1) finds that the normal tonus of the hind limbs of the frog and of the cat disappears when the rami communicantes of the sympathetic ganglia are cut.

If this be so, it seems that stimulation of the sympathetic should produce tonic contraction of the muscles. In some experiments in which I stimulated the sympathetic of the frog for another purpose, I did not observe any effect of this kind, but experiments should be made, both on the frog and on the cat, for the special purpose. In a further paper, De Boer (1914, 2) finds that rigor mortis is more marked on the normal side than on that in which the sympathetic rami have been cut. This result suggests that the tonic state is associated with difficulty of removal of the products of metabolism. The same investigator (1913, 2, and 1914, 1) brings the prolonged contraction, caused by a single induction shock to a veratrinised muscle, into connection with ' the normal tonic state. The electrical state corresponding to this veratrine contraction is that of a prolonged steady negativity of the longitudinal surface to the tendon, as if a continuation of the normal brief state of negativity. De Boer thinks that the prolonged contraction is due to the " sarcoplasm," as suggested by Bottazzi, and similar to that of smooth muscle. A difficulty in this interpretation of the veratrine curve is that a stimulus to the spinal cord, after section of the sympathetic rami, produces a prolonged contraction in a veratrinised frog. De Boer suggests that the accessory endings of Boeke might be directly stimulated by the initial ordinary twitch.