A Proposed Mechanism of Extracellular Regulation of Muscle Composition *

The changes in muscle composition which occur in disturbances of extracellular electrolyte composition were systematically described by Darrow, et al.8"' and confirmed by others.7"8 However, the mechanism responsible for these changes has not been satisfactorily elucidated. It is the purpose of this paper to describe briefly the composition of muscle in the major disturbances of acid-base balance and to present a general theory of the mechanism of electrolyte transfer between cell and extracellular fluid which could account for these findings. It is important to note that relatively little of the data to be discussed subsequently was obtained by the authors and their contribution is simply the interpretation of these data. Muscle electrolyte composition is usually expressed in terms of the fatfree solids (FFS) rather than as concentration per liter of intracellular or extracellular fluid. Since the quantity of muscle solid per kilogram of animal is relatively constant and not affected by changes in extracellular volume, analysis of muscle expressed in these terms permits valid comparison of data obtained in various disturbances. The results of acute experiments are not given since time must elapse before marked alterations in muscle composition occur. The analyses presented are those of skeletal muscle of rats only. Analysis of human muscle obtained by biopsy suggests that changes in cell composition in man are similar.'6 Metabolic alkalosis of the extracellular fluid produced either by administration of sodium bicarbonate or loss of chloride in excess of sodium leads to characteristic changes in muscle composition (Table 1).7,8 The potassium content is low, averaging 38mM/100g.FFS and the intracellular sodium content is elevated, 7.7mM/lOOg.FFS. In addition, there is probably a rise in the concentration of undetermined anion (possibly lactate) in the serum as calculated from the difference between the concentrations of sodium and the sum of the concentrations of chloride and bicarbonate even when the quantity of undetermined anion is corrected for the change in base binding capacity of blood proteins with change in pH. Metabolic acidosis of the extracellular fluid produced either by administration of HCI or NH4C1 or loss of sodium in excess of chloride leads to