The modifications which drugs produce in the functions of the animal body and of its parts are so numerous and varied that we are unable fully to explain them on the basis of our present physiological knowledge. The results of pharmacological experiments furnish us indeed with a number 0r additional facts regarding the functions of organs and tissues which will ultimately lead us to a more correct and thorough knowledge of their physiology. At present, however, we can only explain them hypothetically, and, indeed, in many cases we can do little more than guess at the explanation.

The advantage to be gained from hypothetical explanations is that hypotheses not only lead to further experiment, but serve as guides for experiments, by which, if false, they may be soon disproved, or, if true, may be maintained.

The disadvantage of hypotheses is that they are sometimes apt to be taken for facts, and being made use of as bases for further speculation, may lead more and more astray from the truth. While bearing in mind the danger of speculation, it may be useful to make some guesses at the mode of action of drugs upon the muscle as guides to further research.

The most striking point about muscle is the motor function which it exercises by contracting, and the nature of its contraction must engage our attention. Throughout the universe we find that motion of nearly all sorts resolves itself into a series of vibrations, and the question arises whether the motion of muscle cannot be explained in the same way. .

When a muscle is stimulated it contracts and relaxes once, describing a wave-like curve upon the revolving cylinder. Frequently this first wave is followed by a second, and sometimes even by a third, which are usually ascribed to the simple elasticity of the muscle. Sometimes we can notice that the single contraction wave appears really to consist of two or more partially superimposed on each other, and sometimes we may find two distinct waves arise from one stimulation.

When a muscle is in a state of tetanic contraction it appears to the eye to be perfectly quiet, yet we know that during this period of apparent rest the muscle is in a state of vibration, alternately tending to contract and elongate. These vibrations may succeed one another with a rapidity such that the muscle appears to the eye to be motionless, while a tracing taken upon the revolving cylinder shows distinct successive waves. If the vibrations are still more rapid, the waves may disappear, and we get the muscle describing a straight line. But even when a muscle is entirely relaxed, its parts may be in a state of vibration quite as continuous as in tetanic contraction. This is seen by examining muscular fibre under the microscope. The phenomenon which then presents itself was described by Porret and is often known by his name. On passing a constant current through a thin muscular slip a contraction is seen when the current is closed. During the whole time of the passage of the current, the muscle, to the naked eye, appears to be perfectly at rest, but under the microscope its parts are seen to be in constant motion, presenting an appearance almost exactly similar to the waving of a field of corn on a windy day, or to the motion of rows of cilia. At the same time an actual transference of material takes place in the muscle : the end next the positive pole growing smaller, and the end next the negative pole growing larger. When the current is suddenly reversed, a sudden contraction of the whole muscle takes place, and it then returns to apparent rest; but microscopic observation shows the same cilia-like motion as before, but in an opposite direction.

This phenomenon reminds one very strongly of the crowding together of carriages in a railway train when it is set in motion or stopped by the locomotive pushing behind or stopping in front. We know that the apparent steady movement of the train is due to the backward and forward vibration of the piston in the cylinders of the locomotive, and the question occurs whether the contraction of the muscle as a whole at the moment of opening and breaking the current, is not due to an interference with the rhythmical vibration of its parts. The question also arises whether these vibrations are not to a great extent dependent upon the molecular weight of its constituents. This seems to a certain extent to be indicated by the curious relations between the effects of the alkalis, alkaline earths, and certain metals upon muscle. Thus Cash and I have found that potassium and calcium neutralise the action of each other upon muscle, and if the hypothesis just expressed be correct we should expect that metals having a similar molecular weight to a mixture of calcium and potassium would have no action upon muscle. This appears to be the case. In researches made in Professor Schmiedeberg's laboratory, Anderson Stewart found that nickel and cobalt had no action upon muscle, and White found that tin also had little or none. On comparing then the atomic weights of potassium (39), calcium (40), nickel (59), cobalt (59), and tin (118), we get the following relationships :

K2 (78) + Ca (40) = Ni2 (118), or, CO2 (118), or, Sn (118.)

Sodium in large doses lengthens the curve and increases the contracture when applied to a normal muscle. It adds to the length of the long curves caused by calcium and strontium. Rubidium in large doses produces a long curve with enormous contracture almost like that of barium. One would naturally have expected that the rubidium and barium would have increased each other's effect like sodium, calcium, or strontium; but the reverse is the case, for the abnormal curve caused by rubidium is reduced to the normal by the application of barium. If barium be applied to a greater extent than is sufficient to antagonise rubidium, it first abolishes the prolonged rubidium curve, reducing it to the normal, and then again elongates it, producing its own characteristic curve. Calcium and strontium, which also prolong the curve, though to a less extent than barium, do not antagonise one another's effect - they rather increase it; but calcium reduces the barium curve to the normal before causing its own peculiar curve. At first sight these results seem to be independent of any rule, but a curious relation is to be observed between the atomic weights of these substances. Thus we have seen that rubidium in large doses has the same effect as barium in causing a veratrine-like curve, but barium destroys the effect of rubidium before producing its own effect. On comparing the atomic weights of these elements we find that eight atoms of rubidium have nearly the same weight as five of barium, and by subtracting one from the other we get almost no remainder. Thus,

Ba 137 x 5 = 685 Rb 85.4 x8 = 683.2

Potassium is, as we know, an important constituent of muscle, and it seems possible that the reduction in the barium-curve which calcium causes may be due to their union having resulted in a substance whose molecular weight is a multiple of that of potassium. Thus,

Ba 137 x 2 = 274 - Ca 40 = 234

K 39x6= 234

The alterations which occur in voluntary muscle from the action of such substances as calcium or barium appear to approximate it to some extent to involuntary muscle. Voluntary muscle is chiefly characterised by sudden and rapid contraction and relaxation. Involuntary muscle usually contracts and relaxes slowly. In the slowness of its relaxation, at least, the muscle poisoned by barium or calcium approaches involuntary muscle.

The power of summation which contractile tissues possess is strongly suggestive of the idea that rhythmical vibrations of gradually increasing intensity are going on within the tissue even before any movement becomes visible. A pendulum very gently struck at proper intervals will gradually begin to oscillate through a larger and larger arc. If touched on one side while oscillating, the effect of the touch will depend upon the time at which the touch is applied, for at one period of oscillation it will tend to impede, and at another to assist the oscillation. Possibly some unseen rhythm in the muscle itself may be the cause of the curious variations in excitability observed in dying muscles and in muscles poisoned by lead. Two pendulums connected together will swing harmoniously if their rate of oscillation is the same, but if one be loaded so as to alter its rate of oscillation they will interfere with each other. Possibly the effect of poisons in paralysing nerves may be due rather to alteration in the relative rhythms of the nerve and muscle than to any specific destructive power on the terminations of the nerve itself.

The opposite effects which Gaskell has noticed the vagus nerve and a weak induced current to produce upon the conducting power of the cardiac muscle, sometimes increasing and sometimes diminishing it, may be due to the interference or coincidence of rhythm such as are discussed more fully farther on under the head of Inhibition.

It is impossible to say at present what the true cause of the curious rhythmical contractions of voluntary muscle is, but if we suppose that there is a transverse as well as a longitudinal contraction in muscle, we might regard the rhythmical contractions as resulting from the action of these two opposing forces.

It must be borne in mind that the considerations contained in this section are purely hypothetical, and their only use is to indicate the direction in which we may possibly look for an explanation of the action of medicines on muscle.