The Nature of the Sodium and Potassium Balance in Nerve and Muscle Cells

Abstract

Discrepancies in the membrane theory of K accumulation in muscle and nerve cells led us to re-examine the behaviour of these tissues when soaked in Ringer's solution under various conditions. This work gained further impetus from the recent paper of Ling (19o'2), who has postulated a selective ionic adsorption to account for the high K content of these tissues.The use of radioactive isotopes has disproved any theory involving specific ionic impermeabilities. Subsequent to this, the principles underlying the accumulation of K have centred around the Donnan principle, supplemented by the concept of a Na pump (Dean, 1940; Eccles, 1953).The main consequences of this hypothesis (apart from electrical phenomena, which will be considered in a later paper) are: (i) the ratio of internal to external K should vary with the external concentration according to a Donnan equilibrium, (ii) K movements into or out of the cell should be balanced by Na movements in the opposite direction, or anion movements in the same direction, (iii) when the cell is dead (and there is no energy to maintain the Na pumj)) the cell should eome to ionic equilibrium with its surrounds, i.e., Na in/Na out = Kin/Kout and is greater than 1.That these three criteria are not fulfilled will be evident from the work reported in this paper. This has also been shown by Solomon (1952), who stated on thermodynamic grounds that K movements could not passively result from active Na movements. Lastly, Harris and Maizels (1951) liave demonstrated that none of the above criteria apply in the ease of the human erythrocyte; i.e., the external concentration of K, within wide limits, has little influence on the concentration of eell K attained after 20 hours; the rate of change of Na content is greater than that of K content, and finally, when the cell is dead, the ratio of external K to internal K only rises to about 0-5 after 4 weeks' standing.To aeeount for their findings, these authors (and others) postulate the existence of one or more carrier mechanisms for the transport of these ions, and in most cases an attempt is made to link the Na and K shifts.In this paper we have tested the consequences of the carrier theory either by itself or in conjunction with the Donnan postulates. Our results have led us to discard both these hypotheses and have indicated that a more plausible AoBtraL J. exp. BioL (105S), 33, pp. 153-178.

The Relationship Between Sodium, Potassium, and Chloride in Amphibian Muscle

“…As was found in the unequilibrated series there was no change in K + levels. The relation of this Na + extrusion to the Steinbach (32) "pump" was discussed previously (25). This work has recently been confirmed by Van der Kloot (17).…”

“…The suggestion that K + is adsorbed by the cell is not new (for literature see reference 25). It is no more unreasonable to assume that ionic differentiation takes place in the cell interior than that it happens within the mural structure.…”

Cation Accumulation by Muscle Tissue: The Displacement of Potassium by Rubidium and Cesium in the Living Animal12

“…Selective binding of cations by fixed negative charges inside the cell has already been proposed as a mechanism for the normal accumulation of intracellular potassium (27). This hypothesis gains some support from the recent observation that relatively high concentrations of potassium are apparently maintained in frog muscle which has been soaked in potassium-free 'Ringer solution and poisoned with cyanide plus iodoacetate (25). On the other hand, selective binding of cations within the cell would be expected to result in significant reductions in tissue osmotic activity as intracellular potassium is displaced by cations like rubidium or cesium, for which the fixed negative charges have a higher affinity.…”

“…(23), which indicate the existence of an active inward transport system for potassium which can operate without the simultaneous efflux of sodium. No direct experimental evidence for the active and independent uptake of potassium by muscle has yet appeared, but this concept is at least consistent with the fact that movements of sodium and potassium in and out of muscle do not always occur simultaneously and in a fixed stoichiometrical relationship (3,24,25) as might be expected if potassium accumulation were entirely and directly dependent upon a "sodium pump." It has recently been pointed out that the concentration ratio for potassium in frog muscle somewhat exceeds that predictable simply from the transmembrane potential difference, further suggesting the possibility of some active chemical force responsible for potassium accumulation (26).…”

The Relation Between External Potassium Concentration and the Electrolyte Content of Isolated Rat Muscle in the Steady State*

“…Under either of these latter possibilities, the distinctive shape of the curve could be determined by a saturation phenomenon. A similar explanation could also apply if potassium accumulation were the result of the specific attraction of potassium to fixed negative charges inside the cell (15)(16)(17)(18).…”