Other experiments by Loeb showed that if the voluntary muscle of a frog be immersed in a pure NaCl solution, rhythmical twitchings appear which continue for many hours, or even for days. If, however, a small quantity of CaCl2 be added to the NaCl solution the twitchings cease, although the muscle remains alive in this mixture longer than it does in pure NaCl. Similar results were obtained with solutions of the sodium salts which precipitate calcium, fluoride, oxalate, carbonate, phosphate, etc. In all of these solutions twitchings developed in the muscle. Magnesium and strontium act like calcium in inhibiting the muscular twitchings produced by sodium salts. These experiments led Loeb to the conclusion that the presence of calcium in the body keeps the voluntary muscles from constantly twitching or beating rhythmically in the way the heart does. Calcium, magnesium, and strontium seemed to have a definite inhibitory action on the muscular contractions.
Loeb further showed that the center of a jellyfish (Gonionemus), which when isolated from the margin will not contract in sea-water, will beat rhythmically if placed in pure NaCl solution. If a quantity of CaCl2 or Ca(NO3)2 be added to the NaCl solution the contractions are inhibited. Magnesium and strontium behave in this respect like calcium. If also a sufficient quantity of a calcium precipitating solution (sodium fluoride, phosphate, etc.) be added to sea-water in which the center will not beat, rhythmical contractions soon appear, due apparently to the removal of the calcium from the sea-water and the tissue. In these experiments, as in those with voluntary muscles, calcium, magnesium and strontium have apparently an inhibiting action on muscular contractions.
Loeb has recently made experiments on a jellyfish of the Pacific (Polyorchis) with results which are somewhat different from those described for voluntary muscles and Gonionemus. He found that the normal swimming movements of the uninjured animal could not occur in solutions which did not contain some proportion of magnesium, and the presence of magnesium in the sea-water seemed to be the stimulus for the apparently spontaneous movements of the animal. Calcium and potassium were found to oppose this action of magnesium. Further with the isolated center of Polyorchis, which will not beat in pure sugar solution or in sea-water, it was found that the addition of CaCl2, SrCl2, or BaCl2 to either solution caused contractions to appear. Magnesium chloride did not produce this effect. In pure NaCl solution also the isolated center will not beat, or beats only after a long time, while the addition of CaCl2 to the NaCl causes it to beat at once.
Lingle[53] made experiments with the ventricle of the tortoise heart, which was able to beat for only a short time in pure NaCl solutions. When a small amount of CaCl2 is added, however, the heart may continue to beat for a long period. Lingle explained this by the assumption that NaCl is a poison and that calcium acts in an antitoxic way, a suggestion already offered by Loeb.
Loeb’s experiments on the inhibition of muscular twitchings in voluntary muscles by calcium and magnesium, as well as the similar results he obtained with the isolated center of Gonionemus, led me to test the action of these two substances on the rhythmical movements of the mammalian intestine. It was found that not only the normal movements of the intestine, but also those produced by the saline purgatives such as sodium citrate, sulphate, tartrate, etc., could be very definitely inhibited by the administration of calcium or magnesium chloride. This was the case when these latter substances were given in any way either intravenously, subcutaneously, or applied directly to the serous surfaces of the intestine. The following experiments will illustrate this inhibitory action.
A rabbit was anaesthetized by a subcutaneous injection of 4-5 c.c. 1% morphine solution. The intestines were then carefully exposed and protected in every way from loss of heat and moisture. The method suggested by van Braam-Houckgeest[54] of opening the abdomen under the surface of sodium chloride solution is perhaps the most perfect. A small quantity of m/6 sodium citrate solution (for a rabbit weighing 1,200 g. 2-3 c.c. is sufficient) was injected into a vein of the ear. The intestines almost immediately began to move actively. There was then injected 3-4 c.c. m/6 CaCl2 solution. The intestines within 2 or 3 minutes came entirely to rest and remained perfectly quiet. A second injection of a somewhat greater quantity of sodium citrate caused them to again become active.
A still more striking experiment may be made by exposing the intestines and pouring a small quantity of sodium citrate solution on their peritoneal surfaces. Immediately they become extremely active. If now they be washed off with a little NaCl solution and a few c.c. of a solution of calcium chloride be poured on them they will come to rest at once. These solutions must be at body temperature and isotonic with the blood. If the loops which have been quieted by CaCl2 are again moistened with the citrate solution they will be set into motion as before, and a subsequent application of CaCl2 will again cause all movement to cease. This may be continued almost indefinitely. I have set the same loops in motion and stopped them by these solutions as many as sixteen times in succession.
Magnesium chloride acts in this respect like calcium chloride, and a similar but slighter action is possessed by strontium chloride. Magnesium sulphate has a purgative action just as many other sulphates have. Magnesium citrate also acts in the same way as other citrates. The action of the magnesium in these cases seems to be subordinate.
In addition to the inhibitory action of calcium and magnesium on the peristaltic movements of the intestine, these substances also suppress the secretion of fluid into the intestine. This is shown in the previous chapter (IV), where tables are given to show the course of the experiments. According to these experiments, the normal rate of secretion in an isolated loop was measured. The quantity of fluid secreted was small, but the application of CaCl2 or MgCl2 to the serous surface of the loop stopped the secretion entirely. The subsequent application of sodium citrate caused it to flow again.
In its counteraction of the effect of saline purgatives, calcium behaves in the same way. The increased peristalsis or secretion caused by sodium citrate, sulphate, etc., is entirely suppressed by the administration of calcium or magnesium chloride. This is not true to the same extent of those activities produced by barium chloride. CaCl2 as far as I have been able to determine only partially counteracts the effect of BaCl2. That an antagonism does exist cannot be doubted, but the violent peristaltic movements brought about by BaCl2 cannot be fully suppressed by CaCl2 or MgCl2. As mentioned above, BaCl2 in extremely small doses causes an increased flow of urine.[55] This can be partially inhibited by CaCl2. With slightly larger doses of barium, the flow of urine often ceases abruptly, due probably to the contraction of the musculature of the urinary passages, or possibly to a contraction of the blood vessels of the kidney. This condition is relieved by the administration of CaCl2, that is, the calcium merely counteracts the effect of the barium on the musculature of the urinary passages or blood vessels, whichever it may be.