We have previously described three individuals with a syndrome characterized by hypomagnesemia, hypokalemia, alkalosis, and impaired renal conservation of potassium and magnesium.' This disorder is not associated with an excess of known mineralocorticoids. The urinary excretions of aldosterone, 1 l-hydroxycorticoids, and 17-ketosteroids are not elevated. Aldosterone secretion rates measured in two individuals are high normal but appropriate to their sodium intakes and clinical status. Furthermore, the plasma renin activity is not suppressed but is clearly elevated in all. The basic features of their disorder will be reviewed, emphasizing those aspects that relate to magnesium deficiency in man.Two of the patients are sisters and both are presently well except for complaints related to a chronic, nonspecific dermatitis of many years duration. The skin is thickened with a purple-red hue that is reminiscent of the erythema commonly associated with experimental magnesium depletion in the rat. Both sisters have experienced transient episodes of muscle weakness but otherwise have noted n o symptoms directly attributable to their chemical abnormalities.The occurrence of an unusual syndrome in two siblings prompted an evaluation of their family. The family pedigree is displayed in FIGURE 1. It is noteworthy that their parents are distantly related through a common male ancestor; however, we were unable to demonstrate any similar abnormalities in the other members of the family. The concentration of potassium and magnesium in plasma was normal in the individuals marked by asterisks. Moreover, the patients' parents, their unaffected sibling, and one of their children responded normally to magnesium and potassium restricted diets.The third patient with this syndrome is an unrelated female of similar appearance. No consanguinity was established between her parents, and no similar chemical abnormalities were observed in her immediate family.All three individuals demonstrate an impaired renal conservation of potassium. A representative study is displayed in FIGURE 2. Normal individuals respond to moderate potassium restriction by promptly reducing their urinary excretion of potassium to a level equal to their oral intake. In contrast, the urinary excretion of potassium was significantly greater than the dietary intake in these affected individuals despite their associated hypokalemia.The renal conservation of magnesium was evaluated in a similar fashion, employing a diet that contained approximately 1 mEq of magnesium per 24 hours. These results are tabulated in FIGURE 3. The response of four normal volunteers has *

Summary. The relation between the active potassium influx in the human red blood cell and the extracellular potassium concentration does not appear to be consistent with the Michaelis-Menten model, but is adequately described by a model in which two potassium ions are required simultaneously at some site or sites in the transport mechanism before transport occurs. The same type of relation appears to exist between that portion of the sodium outflux that requires the presence of extracellular potassium and the extracellular potassium concentration. Rubidium, cesium, and lithium, which are apparently transported by the same system that transports potassium, stimulate the potassium influx when both potassium and the second ion are present at low concentrations, as is predicted by the two-site model. IntroductionThe human red blood cell concentrates potassium and extrudes sodium against electrochemical gradients. The magnitude of both the active potassium influx and of a portion of the sodium outflux is a function of extracellular potassium concentration. The form of this relation has

Studies of experimental magnesium depletion have been reported in the past (1)(2)(3)(4)(5)(6)(7)(8). This report describes a re-evaluation of this problem in which some of the previous observations have been confirmed and extended. In particular these studies were concerned with the interrelationships between magnesium deficiency and the metabolism of potassium, calcium, and phosphorus. In addition, the pathologic alterations of the kidneys were examined. These latter observations will be alluded to here, although they have been reported in an abstract (9), and will be the subject of a more detailed discussion in another publication. METHODS A-ND EXPERINIENTAL D)ESIGNFemiale Sprague-Dawley rats were used throughout. The animals were pair-fed by groups a synthetic diet free of sodium, potassium, chloride, phosphate, and magnesium. The composition of this diet is listed in Table I. In additon, each animal received daily by gavage an approp)riate electrolyte solution which will be described in specific terms later. Demineralized water was allowed at will.At the end of each experiment the animals were anesthetized with hexobarbital sodium administered intraperitoneally, and then exsanguinated from the abdominal aorta. Thigh, leg, and lumbar muscles were taken for chemical analysis, and the other tissues obtained for histologic examination. In some experiments total carcass was also analyzed. The preparation of erythrocytes for analysis involved an initial centrifugation in a plastic tube, followed by the removal of plasma and buffy coat. The red cell mass was then recentrifuged at 20,000 g for 15 minutes. At the end of this time the tube was frozen, and then a cut was made just below the top of the erythrocyte mass. In this fashion a quantity of relatively pure red cells was obtained.The chemical methods were as follows: urea nitrogen vith the autoanalyze.r utilizing the calorimetric reaction with diacetyl monoxime (10); sodium and potassium,

No abstract

The effect of graded degrees of K depletion on the ability to produce a concentrated urine was studied in Sprague-Dawley rats. With increasing degrees of K depletion, as measured by the concentration of K in fat-free skeletal muscle, there was a progrossive decrease in the maximum urinary concentration. This defect of the renal concentrating mechanism appeared to be better correlated with the degree than with the duration of potassium depletion and could be demonstrated either by the use of exogenous vasopressin or by water deprivation. The potassium-deficient rats in at least one experiment developed a significant polydipsia. The data do not allow any conclusions with respect to the relationship of the polydipsia to the renal concentrating defect except that the latter at least was not severe at the onset of the increased water intake.