Constant Sodium Research Articles

Ionic dependence of sodium currents in squid axons analyzed in terms of specific ion "channel" interactions.

Inward sodium currents were measured from voltage-clamped giant axons externally perfused with artificial seawater (ASW) solutions containing various concentrations of sodium and potassium ions. The data was analyzed under the assumption that under a constant membrane potential sodium conductance is determined by a specific ion-channel site (SIS) reaction. The sodium current density values were expressed in terms of SIS-reaction rates which were compared, by means of minimization techniques, with those computed for various saturation reaction mechanisms. The following conclusions were drawn: 1) The dependence of peak inward sodium current on external sodium and potassium concentrations can be described in terms of saturation reactions. 2) The experimental data fit well the kinetics of a positive cooperative homotropic reaction, involving at least two allosteric active sites. One of these sites may be catalytic while the other, either catalytic or regulatory. 3) The inhibitory effect of external potassium on inward sodium current, can be described by a reversible competitive or noncompetitive inhibition mechanism. The values of the dissociation constant of the inhibitor-site "complex" (Ki) were found to be close to the external potassium concentration under physiological conditions.

Premicellar and micellar aggregation in sodium octanoate solutions

The premicellar association and the formation of micelles in sodium n-octanoate (NaB) solutions have been investigated by potentiometric titration at constant sodium concentration [3 M Na(Cl)] and by light-scattering photometry in 3 M NaCl, NaBr and NaI. The potentiometric results were treated using the Letagropvrid method. The following stability constants were found: B − + H 2 O = HB + OH − − logβ 1,1 = 8.965 ± 0.019 5B − + H 2 O = HB 5 4− + OH − − logβ 1,5 = 2.196 ± 0.027 9B − + H 2 O = HB 9 8− + OH − − log& = − 1.267 ± 0.199 9B − = B 9 9− − logβ 0,9 = −7.963 max − 8.319. The data can be reconciled satisfactorily, however, with any micellar aggregation number between 9 and 17. The light-scattering measurements followed Huisman's method and yielded a micellar weight of 4.62 ± 0.05 kg mole −1. To reconcile this result with the potentiometric aggregation numbers it is necessary to assume that the micelle binds 6–10 molecules of water per octanoate molecule. This assumption is supported by other investigations.

Effect of proportional reduction of sodium intake on the adaptive increase in glomerular filtration rate/nephron and potassium and phosphate excretion in chronic renal failure in the rat.

1. The influence of dietary sodium intake on the glomerular filtration rate (GFR/nephron) and potassium and phosphate excretion was examined at three stages of progressive chronic renal failure produced in rats by sequential partial nephrectomies. 2. The adaptive increased sodium excretion per nephron in the control group receiving a constant sodium intake did not occur in the experimental group that had a gradual reduction of dietary sodium in direct proportion to the fall in GFR. 3. Despite the difference in sodium excretion, the increase in GFR/nephron, the daily variation in the amount of potassium and phosphate excreted, the increase in potassium and phosphate excretion per unit nephron, and the plasma potassium and phosphate concentrations were the same in the two groups. 4. The concept of 'autonomous adaptation' in chronic renal failure is presented.

OUR EXPERIENCE WITH THE RADIOIMMUNOASSAY OF PRA AND ANGIOTENSIN II IN CHILDREN

We determined PRA and Angio II (Kit of CEA-CEN-SORIN) in some hundred cases in two different technical conditions: (A) pH = 7; DFP as inhibitor (B) pH = 5.5 and BAL-IC. Results: in a group of normal children at normal and constant diet PRA was: 0.64 ± 0.46 ng/ml/h. In 30 infants (8 h. – 11 m.) the mean value was: 0.75±0.27. The correlation between PRA and Angio II values (107 children) was highly significant; in spite of this we no longer measure Angio II with the kit because of the cross reactivity with the hepta and hexapeptide. (B) at pH = 5.5 the PRA values were higher. In 10 normal children (5–12 years) at a constant sodium intake of 50 mEq/m2/day, the mean PRA value in supine position after overnight fasting and rest was: 1.11 ± 0.36; after 30–40 min. exercise was: 2.88 ± 0.34. The previous experience (A) of independence of PRA from hypertension, azotemia etc. was confirmed. The sodium intake and position playan overwhelming role in determining the height of PRA values. Finally, the results obtained in some selected conditions or pathological cases are reported.

The mechanism of the natriuresis of fasting.

This study tests the hypothesis than obligatory cation coverage of metabolicaly generated anions is the mechanism for the sodium diuresis of fasting. Nine obese female subjects were equilibrated on a constant sodium and caloric intake and then fasted while sodium intake was maintianed. Particular activity schedule during fasting as during control. Consecutive 3-h increases in urinary sodium , ammonium, and potassium excretion during fasting were matched against simultaneously determined increases in organic acid anions (OAS) and H2PO4 minus, which would exist in combination with the cations. The changes were significantly correlated (r equals 0.891, P less than 0.001) in the relationship y equals 0.73x plus 19 where y equals increases in organic acid salts plus H2POJ minus and x equals increases in cations. As ammonium excretion rose, sodium conservation occurred with ammonium replacing sodium at the major urinary cation. Corollaries to the hypothesis were also found to be true. They were: (a) Increases in ammonium excretion lagged considerably behind increases in OAS plus H2PO4 minus during the diuretic phase making sodium coverage necessary. (b) Sodium loss was much greater than chloride although chloride balance was minimally negative. (c) After refeeding with glucose, sodium excretion promptly decreased and appeared best correlated with simultaneous decreases in OAS. Ammonium excretion also fell but much less than sodium. The data support the hypothesis that obligatory cation coverage of metabolically generated aniuns is a major mechanism responsible for the sodium diuresis of fasting.

The Mechanisms by which Sodium Excretion is Increased during a Fast but Reduced on Subsequent Carbohydrate Feeding

1. The excretion of electrolytes was studied in six obese subjects before, during and after a 7 day fast. 2. Despite a constant sodium intake throughout the study, there was a marked but transient increase in sodium excretion during the fast, and a sharp reduction in sodium excretion on resuming the carbohydrate diet. 3. Fasting was associated with an increase in the excretion not only of sodium but also of potassium, magnesium, calcium, ammonium, titratable acid, chloride, phosphate, sulphate and organic acids. Refeeding was associated with a prompt reduction in the excretion of all ions other than chloride. 4. The patterns of electrolyte excretion indicated that a major factor responsible for the increased excretion of sodium on fasting and for the retention of sodium on refeeding was a failure of ammonium excretion to keep pace with the changing output of organic acid.

The Activity Coefficients of Formate and Hexanoate Ions in Mixed Aqueous Solutions of Sodium Alkanoate and Sodium Chloride at Constant Sodium Molality (3.0 m).

The Activity Coefficients of Formate and Hexanoate Ions in Mixed Aqueous Solutions of Sodium Alkanoate and Sodium Chloride at Constant Sodium Molality (3.0 m).

Negative sodium balance in lithium carbonate toxicity. Evidence of mineralocorticoid blockade.

The patients reported developed lithium carbonate toxicity while being maintained on a constant sodium and fluid intake. Negative sodium balance was observed in both patients coincident with the onset of lithium carbonate toxicity. Negative sodium balance was also observed in lithium carbonate-toxic rats. The renal response to the mineralocorticoid deoxycorticosterone acetate (DOC) was evaluated in groups of control and lithium carbonate-treated rats in order to further explore the renal mechanisms involved in lithium carbonate toxicity. In established lithium carbonate toxicity, a blunted response to the sodium retaining properties of DOC was present. Accordingly, these observations demonstrate a pathogenic cycle in lithium carbonate toxicity. Mineralocorticoid blockade induced by already toxic concentrations of lithium carbonate promotes renal sodium wasting which in turn leads to further lithium carbonate retention and increased toxicity.

Nature of the Transport Adenosine Triphosphatase Digitalis Complex: IV. EVIDENCE THAT SODIUM-POTASSIUM COMPETITION MODULATES THE RATE OF OUABAIN INTERACTION WITH (Na+ + K+) ADENOSINE TRIPHOSPHATASE DURING ENZYME CATALYSIS

Abstract Estimates of initial binding rates for [3H]ouabain interaction with (Na+ + K+)-ATPase were obtained in the presence of ATP, magnesium, sodium, and potassium by using short assay times at 30°. The reactions were terminated by the rapid addition of excess unlabeled ouabain; this did not appear to displace bound [3H]ouabain during subsequent treatment of the suspensions (prior to assay). Initial binding rates were directly proportional to drug concentrations between 0.2 and 2.0 µm [3H]ouabain (30°). When assays were carried out for longer periods in the presence of at least 0.2 µm [3H]ouabain, the rates adhered to pseudo-first order kinetics. Maximal (i.e. at infinite sodium concentration) second order rate constants were 2.2 x 104 s-1 m-1 at 30° and 4.3 x 104 s-1 m-1 at 37°. Hill analyses (plots) for sodium (constant potassium), potassium (constant sodium) and sodium plus potassium (sodium/potassium = 10) activation of (Na+ + K+)-ATPase suggested that ouabain increased the dissociation constant (K0.5) for potassium but had no effect on K0.5 for sodium. Changes in K0.5 for sodium plus potassium activation were less than for potassium, which suggested that sodium modulates ouabain-potassium antagonism during turnover of the enzyme. In the presence of ATP and magnesium, sodium increased and potassium decreased the rate of [3H]ouabain interaction. Kinetic analyses of [3H]ouabain binding rates suggested that sodium and potassium compete for a common site; dissociation constants for sodium and potassium at 37° were 13.7 mm and 0.213 mm, respectively. This relationship predicted the sensitivity (i.e. in terms of inhibition of enzyme activity) of (Na+ + K+)-ATPase to ouabain in the presence of MgCl2, Tris-ATP, and various sodium and potassium concentrations. The relationship did not apply at sodium concentrations less than 10 mm in the presence of 10 mm potassium, which suggested that the validity of the model requires interaction of other cation-binding sites with sodium. The competitive relationship between sodium and potassium may modulate cardiac glycoside interaction with (Na+ + K+)-ATPase.

The association of a humoral sodium transport inhibitory activity with renal escape from chronic mineralocorticoid administration in the dog.

1. Previous studies in dogs given large intravenous saline infusions had shown the presence of an inhibitor of toad bladder sodium transport in jugular venous plasma. In the present study plasma of six dogs on a constant sodium intake was tested for this humoral sodium transport inhibitory (HSTI) activity before and during chronic administration of desoxycorticosterone acetate (DOCA). 2. Renal escape from mineralocorticoid antinatriuresis occurred 2–7 days after beginning treatment with DOCA. No HSTI activity was present in plasma drawn at 9 a.m. during a control period before DOCA administration but it was found in every case on the morning of the day on which escape occurred. A positive correlation was shown between HSTI activity of 9 a.m. plasma and the rate of sodium excretion for the subsequent 24 h period (r = 0·66, P < 0·002). 3. When DOCA administration was continued for several days after escape had occurred in three dogs, oscillations in HSTI activity correlated with oscillations in renal sodium excretion. 4. The degree of antinatriuresis on any given day correlated with the amount of HSTI activity the following morning (r = 0·61, P < 0·0002). This finding suggests that extracellular fluid volume expansion resulting from DOCA-induced antinatriuresis leads to HSTI activity. These results fit the hypothesis that HSTI activity is a natriuretic hormone which plays a role in the mechanism of DOCA escape.

Fasting and refeeding. III. Antinatriuretic effect of oral and intravenous carbohydrate and its relationship to potassium excretion

Volunteers maintained on a constant sodium, potassium, and fluid intake underwent a water diuresis to examine the antinatriuretic effect of glucose after fasting and to determine its relationship to the changes in circulating insulin, free fatty acids, and other substrates that accompany refeeding with carbohydrate. Further studies were performed to observe the relationship between sodium and potassium excretion as influenced by both oral and intravenous glucose in the fed and fasted state. The results indicate that the natriuresis of fasting was readily reversed by intravenous, as well as oral, glucose and that this effect is independent of changes in circulating insulin and free fatty acids. The ingestion of glucose caused a significant decrease in urinary potassium excretion in both the fed and fasted state. This reduced excretion of potassium occurred independently of glomerular filtration rate and sodium excretion but was seen only when plasma potassium declined.

Cell turgor and selective ion transport of Chaetomorpha linum

The littoral alga Chaetomorpha linum is especially able to maintain a constant turgor pressure in the cell by regulating the internal osmotic pressure, if the salt content of the sea water changes. Experiments in artificial isotonic sea water with a constant sodium concentration, but variable potassium concentrations (from 1 to 50 mMol/1) prove, that the decrease or increase of the potassium concentration in the medium (CK a) is an essential cause for this regulation of the turgor pressure besides the change of the osmotic pressure of the medium, which was thought to be the predominant cause till now. In the examined concentration range the ratio CK a to CK 1 (potassium concentration in the cell) depends linear on CK a in the steady state. At low values of CK a (< 10 mMol/1) the decrease in CK 1 is compensated by a reversible sodium uptake only in part, and this leads to partly high changes in the cell turgor pressure, although the osmotic pressure of the medium remains constant. The results are discussed on the basis of carrier models.

Inverse variations of plasma renin activity and renin substrate in normal man.

Abstract. In the control subject, plasma angiotensin production is a linear function of plasma renin content. Upon incubation of this same plasma in the presence of an excess of homologous renin, angiotensin production is finally limited by the plasma content of renin substrate (PRS). By this method, PRS levels were measured and compared with levels of plasma renin activity (PRA), urinary aldosterone excretion, and sweat sodium and potassium content, in sixteen normal human subjects, aged twenty‐five to thirty years, under three defined metabolic conditions: unrestricted sodium intake, salt depletion, constant sodium intake plus administration of desoxycorticosterone acetate (DOCA). 1) Unrestricted Sodium Intake. In these control subjects, in perfect health, there exist important individual differences in PRS levels. The PRS levels seem to be quite constant for a given subject under a given metabolic condition: the levels remained the same after a four month interval for a given subject. 2) Salt Depletion. Activation of the renin‐angiotensinaldosterone system (RAAS), as shown by an elevation of PRA and of urinary aldosterone excretion, is accompanied by a decrease in PRS levels. 3) Constant Sodium Intake Plus Administration of DOCA. Inactivation of the RAAS, as shown by lowering of PRA and of urinary aldosterone excretion, is accompanied by a marked elevation of PRS levels.It would appear that, in human control subjects there exists an inverse relationship between PRS and PRA levels.

Effect of spironolactone on sodium diuresis in non-toxemic pregnancy

The administration of spironolactone in the 30–36th week of pregnancy to 5 nontoxemic women, placed on a low constant sodium intake, caused an increase in sodium excretion. After discontinuance of the drug a rebound occurred.

Lithium-induced changes in electrolyte balance and tissue electrolyte concentration.

Lithium carbonate was administered chronically in low doses (0.2 mEq/day) to rats on constant sodium diets. The changes in external sodium and potassium balance and brain sodium and potassium concentration were compared to those of control animals. Changes in external sodium balance were in some respects similar to those observed in patients treated with lithium. During the 14 day periods of lithium administration, cumulative sodium excretion was always greater in the lithium-treated rats (p<0.01), and brain sodium concentration was consistently decreased (p<0.01). The mechanisms responsible for these changes are discussed and related to a possible mechanism of action of lithium in manic-depressive disease.

The role of autonomous renal mechanisms in the control of sodium and water balance

Experiments performed on totally isolated dog kidneys demonstrate that the kidney possesses intrinsic mechanisms that tend to keep at a constant level blood concentration, plasma sodium, and plasma oncotic pressure; an intrarenal feed-back effect between these parameters and sodium and water excretion is evidenced. The role of this intrarenal effect in the control of total body sodium and water balance is discussed together with other factors involved.

The effects of external potassium and long duration voltage conditioning on the amplitude of sodium currents in the giant axon of the squid, Loligo pealei.

Giant axons were voltage-clamped in solutions of constant sodium concentration (230 mM) and variable potassium concentrations (from 0 to 210 mM). The values of the peak initial transient current, I(p), were measured as a function of conditioning prepulse duration over the range from less than 1 msec to over 3 min. Prepulse amplitudes were varied from E(m) = -20 mv to E(m) = -160 mv. The attenuation of the I(p) values in high [K(o)] was found to vary as a function of time when long duration conditioning potentials were applied. In both high and low [K(o)], I(p) values which had reached a quasi-steady-state level within a few milliseconds following a few milliseconds of hyperpolarization were found to increase following longer hyperpolarization. A second plateau was reached with a time constant of about 100-500 msec and a third with a time constant in the range of 30 to 200 sec. The intermediate quasi-steady-state level was absent in K-free ASW solutions. Sodium inactivation curves, normalized to I(pmax) values obtained at either the first or second plateaus, were significantly different in different [K(o)]. The inactivation curves, however, tended to superpose after about 1 min of hyperpolarizing conditioning. The time courses and magnitudes of the intermediate and very slow sodium conductance restorations induced by long hyperpolarizing pulses are in agreement with those predicted from the calculated rates and magnitudes of [K(+)] depletion in the space between the axolemma and the Schwann layer.

The influence of external potassium on the inactivation of sodium currents in the giant axon of the squid, Loligo pealei.

Isolated giant axons were voltage-clamped in seawater solutions having constant sodium concentrations of 230 mM and variable potassium concentrations of from zero to 210 mM. The inactivation of the initial transient membrane current normally carried by Na(+) was studied by measuring the Hodgkin-Huxley h parameter as a function of time. It was found that h reaches a steady-state value within 30 msec in all solutions. The values of h(infinity), tau(h), alpha(h),and beta(h) as functions of membrane potential were determined for various [K(o)]. The steady-state values of the h parameter were found to be inversely related, while the time constant, tau(h), was directly related to external K(+) concentration. While the absolute magnitude as well as the slopes of the h(infinity) vs. membrane potential curves were altered by varying external K(+), only the magnitude and not the shape of the corresponding tau(h) curves was altered. Values of the two rate constants, alpha(h) and beta(h), were calculated from h(infinity) and tau(h) values. alpha(h) is inversely related to [K(o)] while beta(h) is directly related to [K(o)] for hyperpolarizing membrane potentials and is independent of [K(o)] for depolarizing membrane potentials. Hodgkin-Huxley equations relating alpha(h) and beta(h) to E(m) were rewritten so as to account for the observed effects of [K(o)]. It is concluded that external potassium ions have an inactivating effect on the initial transient membrane conductance which cannot be explained solely on the basis of potassium membrane depolarization.

The effects of exogenous aldosterone on sweat electrolytes: II. Patients with cystic fibrosis of the pancreas

Aldosterone was administered intramuscularly to four adults and seven children with cystic fibrosis while they were maintained on constant sodium, potassium, and fluid intake. The children were studied also during restricted sodium intake. The sweat glands of the children showed an unexpected ability to respond by significantly retaining sodium and excreting additional potassium. Adult patients did not retain sodium, but the increase in potassium excretion was significant. These responses were independent of sweat output. The renal responses of the children with cystic fibrosis were different from those of the adults but similar to those of normal children. The studies support the hypothesis of an abnormality in both the coil and duct of the sweat glands of patients with cystic fibrosis.

The effects of exogenous aldosterone on sweat electrolytes: I. Normal subjects

Six normal children and eight normal adults received exogenous aldosterone intramuscularly while being maintained on constant sodium, potassium, and fluid intake. Both groups showed active sweat gland responses, with characteristics in many ways different from responses of the kidney. The effects were independent of dosage and were reversible with spironolactone. Sweat sodium retention during administration of aldosterone was not necessarily dependent upon a decrease in sweat rate. The renal response to exogenous aldosterone in children was quite different from that of adults, and may be related to age.