Loading of extracted muscle fibers causes a small, sudden lengthening, followed by a slower, plastic extension, which is reversed only by active contraction. Polyphosphates in the presence of Mg strongly accelerate plastic extension, but elastic changes in length remain the same as during rigor. The modulus of elasticity on the average is about 6.2 x 10(7) dynes per cm.(2) This value is about 40 times larger than that of rubber, if compared on a water-free basis. Extension of muscle, therefore, is almost entirely due to plastic deformation. Mg is essential for the softening action of adenosinetriphosphate (ATP) and can produce partial relaxation in the absence of a relaxation factor. After partial removal of bound Mg, ATP causes strong contraction, but only slight softening. The same condition is produced by very low concentrations of ATP in the presence of phosphocreatine. These observations show that during contraction passive mechanical properties may remain essentially like those during rigor. The constancy of elastic extensibility distinguishes contraction produced by ATP from contraction induced by non-specific agents in various fibrous structures and caused by an increase in configurational entropy.

Adenosine Triphosphate↗

PubMed1955

Binding of calcium and magnesium by the contractile elements.

Using a technique for determining Ca and Mg based on Schwarzenberg's method of titration with ethylenediamine tetraacetic acid (EDTA), it was found that glycerol-extracted muscle fibers contain on the average 0.58 millimole Ca and 0.55 millimole Mg per kg. muscle. The fibers take up additional Ca or Mg from dilute solutions of these metals, but in KCl solutions, the excess is exchanged for K ions. Inorganic pyrophosphate (PP) removes part of the bound Mg, no Ca; EDTA removes predominantly Ca, but never more than about one-half the total amount. These results are discussed in relation to previous observations on the effects of PP and EDTA on mechanical properties and contractility of extracted muscle fibers. After the partial loss of bound divalent metals, muscle fibers swell in dilute salt solutions; they also contract slightly and become more translucent.

Calcium↗

PubMed1955

Monophasic and diphasic action potentials of the stomach.

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Action Potentials↗

PubMed1954

Relaxation in extracted muscle fibers.

1. Ethylenediamine tetraacetic acid (EDTA) in low concentrations imitates all the known effects of the relaxation factor ("Marsh factor"). In extracted muscle fibers which have contracted in a solution containing adenosinetriphosphate (ATP), the addition of EBTA causes relaxation, the subsequent addition of CaCl(2), contraction. 2. In fibers which have been briefly immersed in 5 MM EDTA, ATP causes rapid relaxation if Mg is also present. These fibers have essentially the same properties as briefly extracted fibers. Brief immersion into a solution containing CaCl(2) restores at once the original condition. It is concluded that EDTA produces its action by firmly combining with bound Ca, thereby inactivating it. 3. In relaxed muscle fibers not only Ca, but also lowering the concentration of Mg below a critical level, causes contraction. In such fibers Mg in the lowest effective concentrations increases contraction, but the effect reverses above a certain concentration. 4. At 0 degrees Mg in the presence of ATP has a relaxing effect without the relaxation factor. 5. The results indicate that Mg has two distinct effects in the presence of ATP. It causes contraction at low concentrations, but above a critical concentration its relaxing action prevails. The last of these effects is blocked by bound Ca. If the latter is inactivated by EDTA, Mg in sufficiently high concentrations causes relaxation. The action of the relaxation factor can similarly be explained by assuming that it acts as a complexing agent which inactivates bound Ca. 6. Previous evidence that the relaxed state depends on the formation of an enzymatically inactive ATP-protein complex was confirmed. It was found that PP in low concentrations strongly increases the relaxing effect of ATP in briefly extracted fibers.

Adenosine Triphosphate↗

PubMed1954

Interactions between magnesium, pyrophosphate, and the contractile elements.

1. If glycerol-extracted muscle fibers are alternately immersed in solutions of inorganic pyrophosphate (PP) or ethylenediamme tetraacetate (EDTA) and KCl two to three times, PP no longer increases extensibility. The original condition is restored by solutions containing Mg. EDTA prevents completely the softening action of PP, but has no effect in the presence of an excess of Mg. These observations are explained by assuming that PP and EDTA remove bound Mg. Evidently PP has no softening action without Mg. 2. If PP is washed out from muscle fibers by solutions containing Mg, the softening action of PP persists for many minutes, but washing out with KCl solution promptly abolishes the effect of PP. Also, if fibers which have been made refractory to PP are immersed into a solution of PP and then into a KCl solution free of PP for several minutes, the addition of MgCl(2) alone increases extensibility. It is concluded that PP forms a complex with protein. The formation of this complex, however, has no influence on the mechanical properties, unless Mg also is present. 3. In the presence of PP and Mg the viscous resistance of muscle fibers drops with diminishing temperatures.

Diphosphates↗

PubMed1953

The mechanism of muscular relaxation.

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Humans↗

PubMed1953

The control of energy release in extracted muscle fibers.

Tension and P liberation were determined at the same time in glycerol-extracted muscle fibers suspended in ATP solutions. In the relaxed state, produced by ATP in rather fresh preparations, P liberation was low, but somewhat higher than in normal resting muscle. On addition of small amounts of CaCl(2) the fibers gave a strong contraction during which P liberation was on the average about 5 times higher than in the relaxed condition. In aged muscle fibers ATP always produced a strong contraction associated with a high ATPase activity which was not influenced by Ca. The P liberation during a sustained contraction was much smaller in extracted fibers than in normal muscle, but the former maintained tension much more economically than the latter, resembling smooth muscle in this respect. Also the removal of Mg caused a contraction associated with high ATPase activity. Mg, therefore, is inhibitory in relaxed fibers. In fibers activated by Ca or by aging, however, it caused enhancement. The effects of ions on ATPase activity of relaxed fibers are similar to those on myosin and dissociated actomyosin, whereas activated fibers resemble actomyosin at low salt concentration.

Actomyosin↗

PubMed1953

The role of phosphocreatine and adenosinetriphosphate in muscular contraction.

In the presence of 20 mM PC a strong contraction is produced in glycerol-extracted muscle fibers by ATP and AMP in concentrations as low as 10(-6)M per liter. At low concentrations of nucleotide tension rises very slowly. This rise is interpreted as being due to absorption of nucleotide by the contractile elements. AMP gives an S-shaped tension curve, indicating that the conversion of AMP into ATP is an autocatalytic process. Tension is maintained in a contracted muscle even in PC solutions free of ATP. PC alone produces a contraction if applied within 5 minutes after ATP has been washed out from a contracting muscle. It is concluded from these results that PC is the substrate for the enzymatic activity of the contractile elements and that this activity depends on the presence of bound nucleotide which acts as an energy transfer mechanism. PC accelerates relaxation which is caused by ATP under certain conditions. In the presence of PC even very low concentrations of ATP can produce relaxation. A strong contraction can be produced under these conditions by the addition of Ca ions. These observations support the conclusion that relaxation depends on the rephosphorylation of nucleotide bound by the contractile elements.

Adenosine Triphosphate↗

PubMed1952

The effect of electrolytes on the contractile elements of muscle.

The effects of changes in electrolyte concentration on muscles which had been preserved in 50 per cent glycerol or washed in water were studied. The psoas preparation of Szent-Györgyi was generally used, but smooth and cardiac muscle gave the same results. If the preparations are immersed in 0.16 molar NaCl or KCl and if the electrolyte subsequently is washed out with distilled water, tension rises. This effect is not obtained if solutions of CaCl(2) or MgCl(2) are used, but it is restored by brief immersion in NaCl or KCl solutions. Changes in pH have no effect. It is concluded that divalent cations are bound more firmly than monovalent ions, but that divalent exchange with monovalent ions. After the application of ATP washing out electrolytes produces a much larger and more rapid rise in tension. This effect persists after ATP has been washed out and seems to be due to the removal of a substance which diminishes the dissociation of bound cations. Washing out electrolytes also causes a large increase in transparency and swelling. These effects are also enhanced by previous application of ATP and are abolished or diminished by divalent cations. The rise in tension and the swelling are explained as the result of an increase in the charge of the polar groups of the proteins. Because this mechanism produces only a small degree of shortening, it does not explain normal contraction, but it may be a part of this process. The significance of the phenomena described in relation to recent theories of the mechanism of muscular contraction is discussed. The observations show that increase in the charge of the contractile proteins causes contraction, not relaxation, as has been commonly assumed.

Cations, Divalent↗