Potassium Transport In Erythrocytes Research Articles

Erythrocyte ion transport and membrane lipid composition in young and adult rats with NO-deficient hypertension

The aim of our study was to search for abnormalities of sodium and potassium transport in erythrocytes of male Wistar rats subjected to chronic L-NAME treatment (40 mg/kg/day) for 4 weeks either from weaning (4-week-old) or in adulthood (12-week-old). Sodium content, Na +,K +-pump and Na +,K +-cotransport activity, cation leaks as well as membrane cholesterol and phospholipid contents were determined in fresh erythrocytes. Chronic inhibition of NO synthase elicited similar blood pressure rise in both age groups which did not differ in the degree of NO synthase inhibition. No significant ion transport abnormalities were disclosed in erythrocytes of young NO-deficient rats, whereas erythrocyte Na + content, outward Na +,K +-cotransport and inward Na + leak were significantly reduced in adult hypertensive animals compared to age-matched controls. It should be noted that the erythrocytes of adult control rats were characterized by higher activity of Na +,K +-pump and Na +,K +-cotransport, increased Na + and Rb + leaks and elevated membrane cholesterol content compared to those of young normotensive controls. Increased Na + leak and elevated membrane cholesterol content but reduced membrane phosholipid content were revealed in erythrocytes of adult hypertensive rats when compared to young hypertensive rats. It can be concluded that young and adult Wistar rats did not differ in the extent of NO synthase inhibition and blood pressure rise elicited by chronic L-NAME treatment. Our results exclude the important participation of classical sodium transport abnormalities in the pathogenesis of this NO-deficient form of experimental hypertension.

Additional mechanisms of nafamostat mesilate-associated hyperkalaemia.

Nafamostat mesilate, a potent protease inhibitor, is widely used for the treatment of pancreatitis, disseminated intravascular coagulation and as an anticoagulant in haemodialysis. However, hyperkalaemia associated with nafamostat mesilate has been reported. It is thought to be due to decreased urinary potassium excretion, of the drug suppression of aldosterone secretion, and a direct inhibitory action on the apical Na+ conductance in collecting ducts. We have seen two cases of nafamostat mesilate associated-hyperkalaemia, which indicated that extrarenal potassium imbalance might play a role in inducing hyperkalaemia. To examine the effect of nafamostat mesilate on potassium transport in erythrocytes in vitro, 86RbCl uptake was measured in red blood cells from eight healthy volunteers. Nafamostat mesilate and a metabolite, 6-amidino-2-naphthol, at concentrations of 10(-4) and 10(-3) M, respectively, significantly, suppressed potassium influx whilst another metabolite, p-guanidino-benzoic acid, had no effect. The inhibitory action of nafamostat mesilate was not affected by various inhibitors. Nafamostat mesilate and its metabolite, 6-amidino-2-naphthol, suppressed potassium influx in erythrocytes by inhibition of a Na-K ATPase dependent pathway, which was not inhibited by amiloride, barium, nor by frusemide (furosemide).

Reconstitution of Ca(2+)-dependent K+ transport in erythrocyte membrane vesicles requires a cytoplasmic protein.

We have demonstrated that calcium-dependent potassium transport in erythrocytes requires the participation of a cytoplasmic protein. Activation of calcium-dependent potassium transport causes an increase in the membrane-bound levels of this protein which is dependent on the calcium concentration and which is highly correlated (r = 0.791, p less than 0.0001) with the loss of potassium. Reconstitution of this transport pathway in sonicated erythrocyte membrane vesicles was achieved only in vesicles containing the cytoplasmic protein indicating a causal relationship in this transport system. The protein is found in high levels within the cytoplasm of erythrocytes (5.6 mg/ml red blood cells) and yet less than 1% of the protein located in the cytoplasm is required to bind to the membrane in order to initiate the potassium efflux. The analysis of rat organ homogenates demonstrated that this protein is located in most tissues with particular enrichment in adrenal glands, brain, lung, and blood. These results demonstrate that there is a cytoplasmic protein, herein named calpromotin, which is a necessary and sufficient cytoplasmic component of calcium-dependent potassium transport in erythrocytes and perhaps other tissues.

Effects of a chronic high salt intake on blood pressure and the kinetics of sodium and potassium transport in erythrocytes of young and adult subtotally nephrectomized Sprague???Dawley rats

Erythrocyte Na+ and K+ transport mediated by the Na(+)-K+ pump, the Na+,K+ cotransport system and cation leaks, together with blood pressure, were determined in young and adult rats subjected to either chronic salt deprivation or chronic salt loading combined with subtotal nephrectomy. The kinetics of ion transport were studied in Na+ media as a function of extracellular K+, replaced by extracellular Rb+, and intracellular Na+ varied around the physiological range. A high salt intake increased blood pressure in young but not in adult subtotally nephrectomized rats. Erythrocyte Na+ or K+ contents of salt-deprived and salt-loaded rats did not differ. There were no major changes in Na+,K+ cotransport or cation leaks in salt-loaded rats. Chronic salt loading caused some alterations in the kinetics of the Na(+)-K+ pump, which were greater in young than in adult rats. The most pronounced change was a decreased affinity of the Na(+)-K+ pump for intracellular Na+, which was partially balanced by an increased maximal velocity. At physiological (in vivo) ion concentrations these kinetic alterations caused a slight reduction in total ouabain-sensitive Rb+ uptake [partly due to a decrease in intracellular K+:extracellular Rb+ (1:1) exchange] but no changes in Na+ net extrusion in salt-loaded rats. The erythrocyte Na+ and K+ transport systems showed no changes in intrinsic properties that would favour the development or maintenance of salt hypertension in young over adult rats if similar alterations occurred in tissues relevant for blood pressure control.

Lithium, sodium and potassium transport in erythrocytes of manic-depressive patients.

Different Li, Na and K transport pathways were assessed in erythrocytes from manic-depressive patients. No alteration in the Li-Na countertransport, Na,K cotransport or passive permeabilities was observed in either unipolar or bipolar manic-depressive patients. In addition, acute or chronic lithium treatment did not alter the maximal velocity of either the Li-Na countertransport or the Na,K cotransport. A two-fold reduction of the ouabain-sensitive Na efflux was observed among manic-depressive patients without alteration in the affinity of the Na pump for internal Na.

Plasma membrane NADH dehydrogenase and Ca 2+-dependent potassium transport in erythrocytes of several animal species

Ca 2+-dependent K + transport and plasma membrane NADH dehydrogenase activities have been studied in several ‘high-K +’ (human, rabbit and guinea pig) and ‘low-K +’ (dog, cat and sheep) erythrocytes. All the species except sheep showed Ca 2+-dependent K + transport. NADH-ferricyanide reductase was detected in all the species and showed positive correlation with the flavin contents of the membranes. NADH-cytochrome c reductase was very low or absent in dog, sheep and guinea pig membranes. No correlation was found between NADH dehydrogenase and Ca 2+-dependent K + channel activities in the species studied. Nor were any of the above activities correlated with ( Na + + K +)- ATPase activity.

Catecholamine-Stimulated Potassium Transport in Erythrocytes from Normal and Hyperthyroid Turkeys: Quantitative Relation between β-Adrenergic Receptor Occupancy and Physiological Responsiveness*

We have previously shown that erythrocytes from hyperthyroid turkeys are identical to normal turkey erythrocytes with respect to the number and affinity of β-receptors, maximal catecholamine-stimulatable adenylate cyclase activity, and cAMP accumulation. In the present study we now report that despite these similarities, the physiological responsiveness of hyperthyroid cells to catecholamines is markedly altered. Maximal catecholamine-induced stimulation of potassium ion transport in erythrocytes from hyperthyroid turkeys is significantly reduced (21.8 ± 2.4 vs. 34.1 ± 3.0 meq/liter cells-h; P < 0.005). In addition, there is a slight increase in the concentration of isoproterenol required for the induction of half-maximal stimulation (5.7 ± 0.8 vs. 3.9 ± 0.4 nM; P < 0.05). Quantitative assessment of potassium influx in relation to β-receptor occupancy by agonist indicates that despite the absence of any change in β-receptor number, the degree of stimulation of potassium transport per agonist-occupied β-re...

Characteristics of active sodium and potassium transport in erythrocytes in children with different stages of symptomatic uremia.

Erythrocytes from 15 uremic children aged from 7 months to 16 years were analyzed for adenosine triphosphatase (total ATPase and ouabain sensitive ATPase i.e. Na+, K+-ATPase), sodium and potassium ions and ATP concentration, in some cases before and after therapeutic measures had been undertaken. No correlation was found between the levels of Na+, K+-ATPase and serum creatinine and all uremic children had Na+, K+-ATPase levels within the range for normal children. The children with rapidly progressive uremia had higher activities of Na+, K+-ATPase at the corresponding serum creatinine concentration than those with slowly progressive uremia. Longitudinally the Na+, K+-ATPase activities fell and the erythrocyte Na+-K+ ratio increased in slowly progressive uremia. Introduction of a low-protein, high-energy diet giving accelerated growth did not change the Na+, K+-ATPase activities, the concentrations of erythrocyte sodium and potassium ions or ATP. Hemodialysis gave a slight increase of Na+, K+-ATPase and of the erythrocyte Na+-K+ ratio, whereas renal transplantation resulted in a remarkable increase of Na+, K+-ATPase activity and decrease of Na+-K+ ratio. A distinct feature of uremic children with hypertension was a low erythrocyte Na+-K+ ratio and a high Na+, K+-ATPase level.

Characteristics of active sodium and potassium transport in erythrocytes of healthy infants and children.

Erythrocytes were analysed for adenosine triphosphatase (total and sodium-potassium activated) activities, concentrations of sodium and potassium ions and ATP in normal individuals from birth to adulthood age. A decrease of Na+, K+-ATPase activity and an increase of the sodium concentration was seen in infants aged 1-3 and 4-8 months. A decrease of Na+, K+-ATPase was seen during puberty. A correlation was seen between the Na+, K+-ATPase activity and the Na+-K+ ratio. Different influences which might lead to the observed changes in Na+, K+-ATPase activity and erythrocyte sodium concentration are discussed.

Beta-adrenergic receptors and isoproterenol-stimulated potassium transport in erythrocytes from normal and hypothyroid turkeys. Quantitative relation between receptor occupancy and physiologic responsiveness.

We have previously reported that in hypothyroid turkeys the number of beta-adrenergic receptors in intact erythrocytes is reduced by approximately 50% without any changes in the affinity of the receptor for the agonist, isoproterenol. In view of the physiological action of the catecholamines to stimulate bidirectional ion fluxes in these cells, we have now examined the possibility that the decrease in beta receptor number might be associated with concomitant changes in catecholamine-dependent potassium ion transport. Hypothyroid turkey erythrocytes display decreased sensitivity to isoproterenol-stimulated potassium influx. Half-maximal stimulation of potassium influx occurs at 9.2+/-1.7 nM in hypothyroid cells as opposed to only 3.8+/-0.4 nM in normal cells (P < 0.005). A maximal stimulatory concentration of isoproterenol (100 nM) leads to the same increment in ion flux in erythrocytes from hypothyroid and normal turkeys. Analysis of the quantitative relationship between isoproterenol concentration, receptor occupancy, and associated effects upon potassium influx shows that at low levels of isoproterenol, where occupancy is linear with agonist concentration, occupation of a given number of beta receptors leads to a stimulation of potassium transport that is identical in erythrocytes from normal and hypothyroid turkeys. Thus, decreased sensitivity to catecholamine-stimulated potassium transport in hypothyroidism can be attributed to the decrease in receptor number and the resulting two- to threefold higher isoproterenol concentration required for occupancy of the same number of beta receptors. Once a single receptor is occupied, however, the more distal components of the sequence of events mediating the physiological response to beta-adrenergic agonists in the hypothyroid cell function as they do under normal circumstances. It would appear, therefore, that the decrease in sensitivity to isoproterenol-dependent ion flux in the hypothyroid turkey erythrocyte can be accounted for solely by the decrease in receptor number. These changes are shown to occur in the absence of any modifications in the number of Na(+)-K(+) ATPase effector units per cell.

Stoichiometry of sodium and potassium transport in erythrocytes from patients with myotonic muscular dystrophy.

1. 22Na and 42K radioisotopes were used to measure Na efflux and K influx in identical suspensions of fresh erythrocytes from myotonic dystrophy patients and matched controls under the same conditions and in the same time interval. K was present in concentration 10 mM in the suspending medium to prevent Na-for-Na exchange. Each flux was measured in the presence and absence of ouabain. The mean ouabain-sensitive Na efflux rate in controls (2-33+/-0-13, S.E. of mean, m-equiv/1. cells.hr) was significantly greater (P less than 0-001) than the corresponding rate in myotonic dystrophy (1-64+/-0-09). 2. No significant differences between myotonic dystrophy and controls in mean ouabain-insensitive Na efflux, mean ouabain-sensitive K influx, or mean ouabain-insensitive K influx were found. 3. The stoichiometric ratio (ouabain-sensitive Na efflux)/(ouabain-sensitive K influx) was determined for each flux experiment. The mean stoichiometric ratio determined in controls (1-46+/-0-08) reconfirms extensive previous evidence favouring a 3Na-for-2K active exchange in controls. 4. The mean stoichiometric ratio determined in myotonic dystrophy (1-01+/-0-06) is statistically significantly different (P less than 0-001) from that in controls. These findings are interpreted as indication of 2Na-for-2K exchange in erythrocytes from patients with myotonic dystrophy.

Sodium and potassium transport in erythrocytes.

Sodium and potassium transport in erythrocytes.