158 



HANDBOOK OF PHYSIOLOGY 



CIRCULATION I 



Distribution of Sodium and Potassium in Muscle 



It is well known that the main intracellular cation 

 of muscle is potassium, sodium being to a large extent 

 excluded. The actual intracellular concentrations of 

 these ions cannot be stated with certainty because of 

 the variability of the extracellular fluid space measure- 

 ments on which calculations of intracellular values de- 

 pend. For example, total sodium and potassium con- 

 centrations (meq loo g dry tissue) have been found 

 to be the same in both dog and cat ventricle. However, 

 an extracellular space of 18.2 per cent was found with 

 C" mannitol in the dog heart (53); whereas a value of 

 25 per cent was calculated for the cat heart on the 

 basis of chloride measurements (245). The calculated 

 intracellular potassium concentrations were thus 151 

 and 139 meq per liter of fiber water for cat and dog, 

 respectively; and sodium concentrations were 6.5 and 

 21.5 (recalculated from references 53, 245, 335). The 

 variability of extracellular space measurements in 

 the same species can be appreciated by reference to 

 two published results on frog ventricle, one with an 

 inulin space of 19.1 per cent, the other with a sucrose 

 space of 24 per cent (i 10, 158). The problem of ex- 

 tracellular space measurement in cardiac tissue is 

 magnified by the trabecular structure of the organ, 

 which causes difficulty in blotting successive tissue 

 samples uniformly. This factor may be even more im- 

 portant in the atrium with its loosely arranged muscle 

 cells and large surface-to-volume ratio, for which an 

 inulin space as high as 44 per cent has been reported 

 (236). For ventricular tissue, extracellular space 

 measurements based on the distribution of inulin or 

 mannitol (53, 1 10, 134) are in fairly good agreement, 

 and yield calculated intracellular sodium concentra- 

 tions of 23.0, 27.7, and 21.5 meq per liter of fiber 

 water for frog, rat, and dog, respectively. Other refer- 

 ences on the tissue partition of electrolytes in heart 

 may be found in the review by Manery (207) and in 

 papers of Lowry (197), and Darrow el al. (63). 



No categorical answer can be given to the question 

 whether intracellular potassium is distributed uni- 

 formly throughout the cell with a chemical activity 

 equivalent to that of a free solution. .Studies pertinent 

 to the point include binding of potassium to intra- 

 cellular proteins (i8g, 299), exchangeability of radio- 

 acti\e potassium between cells and medium (52, 235), 

 analysis of potassium efflux from cells (121, 122 ), histo- 

 chemical localization of potassium within the cell 

 (65, 90), o.smotic pressure measurements (54), meas- 

 urements of electrical conductivity of protoplasm 

 (141, p. 281), and mobility of radioactive potassium 



in cells under the influence of an electrical gradient 

 (118, 145). 



The binding of potassium to proteins has been 

 studied by numerous investigators (299, p. 37). Lewis 

 & SarofT (189), using an anion impermeable mem- 

 brane, found that at pH 6.4 in 0.15 m KCl, potassium 

 was bound to myosin to the extent of about 12 ions 

 per mole of myosin. Actin and albumin exhibited no 

 potassium binding capacity. Potassium binding by 

 myosin would amount to not more than 5 per cent of 

 the total cell potassium however, and even this value 

 might be less in the presence of cellular divalent 

 cations. 



A number of studies on the e.xchangeabilitv ol 

 radioactive potassium lead to the conclusion that one 

 cannot regard the cell as a simple sac filled with a 

 solution of potassium ions. For example, although it is 

 generally agreed that cellular potassium is completely- 

 exchangeable at body temperature (52, 235), at low- 

 temperatures a portion of the potassium becomes 

 practically nonexchangeable (116, 117, 127, 287). If 

 one portion still exchanges normallv at low tempera- 

 ture while another portion becomes nonexchangeable, 

 an alteration of membrane permeaijility cannot ac- 

 count for the findings; rather it appears that diff'usion 

 of a part of the intracellular potassium ion becomes 

 restricted in the cold for some unknown reason. The 

 work of Harris & .Stcinbach (121, 122) also leads to 

 the conclusion of nonuniform beha\ior of intracellular 

 potassium, since these investigators found that the 

 potassium leached out of cells pre\iousl\- equiliijrated 

 with radioactive potassium had different specific 

 activities — the potassium collected early ha\ing a high 

 specific activity, the value decreasing progressi\-ely 

 in the samples collected later. The nonuniformity of 

 intracellular potassium distribution is also suggested 

 by other evidence. Histochemical studies on the lo- 

 calization of potassium indicate that there appear to 

 be potassium rich zones (63) [for contrary evidence 

 see (90)]. The potassium concentration in certain 

 subcellular particles such as the mitochondria may be 

 different from that of the surrounding system (287). 



Such lines of exidcnce have led several investiga- 

 tors to the \iew tliat the various intracellular ions are 

 not uniformly distributed (119, 192, 275). Harris 

 (119), for example, suggests that there is an outer 

 region of the cell containing nonspecific binding sites, 

 and an inner region with sites normally occupied by 

 potassium. The time course of ion movement will be 

 limited by- inter-site migration and also by long paths 

 of \arious lengths imposed by cellular structures. 



