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. 1976 Apr;57(4):1019–1024. doi: 10.1172/JCI108343

Reversible changes of the muscle cell in experimental phosphorus deficiency.

T J Fuller, N W Carter, C Barcenas, J P Knochel
PMCID: PMC436745  PMID: 947947

Abstract

Both animal and human studies suggest that either phosphorus depletion or hypophosphatemia might have an adverse effect on muscle function and composition. Recently a possible deleterious effect was noted in patients with chronic alcoholism. In this unexplained disease, a variety of toxic and nutritional disturbances could affect the muscle cell, thus obscuring the precise role of phosphorus. Accordingly, we examined eight conditioned dogs for the possibility that phosphorus deficiency per se might induce an abnormally low resting transmembrane electrical potential difference (Em) and alter the composition of the muscle cell. Eight conditioned dogs were fed a synthetic phosphorus-deficient but otherwise nutritionally adequate diet plus aluminum carbonate gel for a 28-day period followed by the same diet with phosphorus supplementation for an additional 28 days. Sequential measurements of Em and muscle composition were made at 0 and 28 days during depletion and again after phosphorus repletion. Serum inorganic phosphorus concentration (mg/100 ml) fell from 4.2 +/- 0.6 on day 0 t0 1.7 +/- 0.1 on day 28. Total muscle phosphorus content (mmol/100 g fat-free dry wt [FFDW]) fell from 28.5 +/- 1.8 on day 0 to 22.4 +/- 2.1 on day 28. During phosphorus depletion, average Em (-mV) fell from 92.6 +/- 4.2 to 77.9 +/- 4.1 mV (P less than 0.001). Muscle Na+ and Cl- content (meq/100 g FFDW) rose respectively from 11.8 +/- 3.2 to 17.2 +/- 2.8 (P less than 0.01) and from 8.4 +/- 1.4 to 12.7 +/- 2.0 (P less than 0.001). Total muscle water content rose from 331 +/- 12 to 353 +/- 20 g/100 FFDW (P less than 0.05). A slight, but nevertheless, significant drop in muscle potassium content, 43.7 +/- 2.0-39.7 +/- 2.2 meq/100 g FFDW (P less than 0.05) was also noted. After 4 wk of phosphorus repletion, all of these measurements returned toward control values. We conclude that moderate phosphorus depletion can induce reversible changes in skeletal muscle composition and transmembrane potential in the dog, and it apparently occurs independently of profound hypophosphatemia.

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Selected References

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  1. Akaike N., Kowa Y. Active transport of sodium and potassium in Na-loaded skeletal muscles of potassium-deficient rats. Jpn J Physiol. 1970 Feb 15;20(1):130–144. doi: 10.2170/jjphysiol.20.130. [DOI] [PubMed] [Google Scholar]
  2. Alberti K. G., Emerson P. M., Darley J. H., Hockaday T. D. 2,3-Diphosphoglycerate and tissue oxygenation in uncontrolled diabetes mellitus. Lancet. 1972 Aug 26;2(7774):391–395. doi: 10.1016/s0140-6736(72)91793-x. [DOI] [PubMed] [Google Scholar]
  3. Bank W. J., DiMauro S., Bonilla E., Capuzzi D. M., Rowland L. P. A disorder of muscle lipid metabolism and myoglobinuria. Absence of carnitine palmityl transferase. N Engl J Med. 1975 Feb 27;292(9):443–449. doi: 10.1056/NEJM197502272920902. [DOI] [PubMed] [Google Scholar]
  4. Bilbrey G. L., Herbin L., Carter N. W., Knochel J. P. Skeletal muscle resting membrane potential in potassium deficiency. J Clin Invest. 1973 Dec;52(12):3011–3018. doi: 10.1172/JCI107499. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. CONWAY E. J. Nature and significance of concentration relations of potassium and sodium ions in skeletal muscle. Physiol Rev. 1957 Jan;37(1):84–132. doi: 10.1152/physrev.1957.37.1.84. [DOI] [PubMed] [Google Scholar]
  6. Craddock P. R., Yawata Y., VanSanten L., Gilberstadt S., Silvis S., Jacob H. S. Acquired phagocyte dysfunction. A complication of the hypophosphatemia of parenteral hyperalimentation. N Engl J Med. 1974 Jun 20;290(25):1403–1407. doi: 10.1056/NEJM197406202902504. [DOI] [PubMed] [Google Scholar]
  7. Cunningham J. N., Jr, Carter N. W., Rector F. C., Jr, Seldin D. W. Resting transmembrane potential difference of skeletal muscle in normal subjects and severely ill patients. J Clin Invest. 1971 Jan;50(1):49–59. doi: 10.1172/JCI106483. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Jacob H. S., Amsden T. Acute hemolytic anemia with rigid red cells in hypophosphatemia. N Engl J Med. 1971 Dec 23;285(26):1446–1450. doi: 10.1056/NEJM197112232852602. [DOI] [PubMed] [Google Scholar]
  9. Kendig J. J., Bunker J. P. Extracellular space, electrolyte distribution, and resting potential in K depletion. Am J Physiol. 1970 Jun;218(6):1737–1741. doi: 10.1152/ajplegacy.1970.218.6.1737. [DOI] [PubMed] [Google Scholar]
  10. Knight A. H., Williams D. N., Spooner R. J., Goldberg D. M. Serum enzyme changes in diabetic ketoacidosis. Diabetes. 1974 Feb;23(2):126–131. doi: 10.2337/diab.23.2.126. [DOI] [PubMed] [Google Scholar]
  11. Knochel J. P., Bilbrey G. L., Fuller T. J., Carter N. W. The muscle cell in chronic alcoholism: the possible role of phosphate depletion in alcoholic myopathy. Ann N Y Acad Sci. 1975 Apr 25;252:274–286. doi: 10.1111/j.1749-6632.1975.tb19168.x. [DOI] [PubMed] [Google Scholar]
  12. Knochel J. P., Schlein E. M. On the mechanism of rhabdomyolysis in potassium depletion. J Clin Invest. 1972 Jul;51(7):1750–1758. doi: 10.1172/JCI106976. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. LEAF A. On the mechanism of fluid exchange of tissues in vitro. Biochem J. 1956 Feb;62(2):241–248. doi: 10.1042/bj0620241. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Leaf A. Regulation of intracellular fluid volume and disease. Am J Med. 1970 Sep;49(3):291–295. doi: 10.1016/s0002-9343(70)80019-5. [DOI] [PubMed] [Google Scholar]
  15. Lichtman M. A., Miller D. R., Cohen J., Waterhouse C. Reduced red cell glycolysis, 2, 3-diphosphoglycerate and adenosine triphosphate concentration, and increased hemoglobin-oxygen affinity caused by hypophosphatemia. Ann Intern Med. 1971 Apr;74(4):562–568. doi: 10.7326/0003-4819-74-4-562. [DOI] [PubMed] [Google Scholar]
  16. Lotz M., Zisman E., Bartter F. C. Evidence for a phosphorus-depletion syndrome in man. N Engl J Med. 1968 Feb 22;278(8):409–415. doi: 10.1056/NEJM196802222780802. [DOI] [PubMed] [Google Scholar]
  17. Nichols B. L., Hazlewood C. F., Barnes D. J. Percutaneous needle biopsy of quadriceps muscle: potassium analysis in normal children. J Pediatr. 1968 Jun;72(6):840–852. doi: 10.1016/s0022-3476(68)80437-8. [DOI] [PubMed] [Google Scholar]
  18. Rosalki S. B. An improved procedure for serum creatine phosphokinase determination. J Lab Clin Med. 1967 Apr;69(4):696–705. [PubMed] [Google Scholar]
  19. Silvis S. E., Paragas P. D., Jr Paresthesias, weakness, seizures, and hypophosphatemia in patients receiving hyperalimentation. Gastroenterology. 1972 Apr;62(4):513–520. [PubMed] [Google Scholar]
  20. Thomas R. C. Electrogenic sodium pump in nerve and muscle cells. Physiol Rev. 1972 Jul;52(3):563–594. doi: 10.1152/physrev.1972.52.3.563. [DOI] [PubMed] [Google Scholar]
  21. Travis S. F., Sugerman H. J., Ruberg R. L., Dudrick S. J., Delivoria-Papadopoulos M., Miller L. D., Oski F. A. Alterations of red-cell glycolytic intermediates and oxygen transport as a consequence of hypophosphatemia in patients receiving intravenous hyperalimentation. N Engl J Med. 1971 Sep 30;285(14):763–768. doi: 10.1056/NEJM197109302851402. [DOI] [PubMed] [Google Scholar]
  22. Vélez-Garciá E., Hardy P., Dioso M., Perkoff G. T. Cysteine-stimulated serum creatine phosphokinase: unexpected results. J Lab Clin Med. 1966 Oct;68(4):636–645. [PubMed] [Google Scholar]
  23. Yawata Y., Hebbel R. P., Silvis S., Howe R., Jacob H. Blood cell abnormalities complicating the hypophosphatemia of hyperalimentation: erythrocyte and platelet ATP deficiency associated with hemolytic anemia and bleeding in hyperalimented dogs. J Lab Clin Med. 1974 Nov;84(5):643–653. [PubMed] [Google Scholar]

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