Internal Sodium Concentration Research Articles

Salt Sensation and Regulation.

Taste sensation and regulation are highly conserved in insects and mammals. Research conducted over recent decades has yielded major advances in our understanding of the molecular mechanisms underlying the taste sensors for a variety of taste sensations and the processes underlying regulation of ingestion depending on our internal state. Salt (NaCl) is an essential ingested nutrient. The regulation of internal sodium concentrations for physiological processes, including neuronal activity, fluid volume, acid–base balance, and muscle contraction, are extremely important issues in animal health. Both mammals and flies detect low and high NaCl concentrations as attractive and aversive tastants, respectively. These attractive or aversive behaviors can be modulated by the internal nutrient state. However, the differential encoding of the tastes underlying low and high salt concentrations in the brain remain unclear. In this review, we discuss the current view of taste sensation and modulation in the brain with an emphasis on recent advances in this field. This work presents new questions that include but are not limited to, “How do the fly’s neuronal circuits process this complex salt code?” and “Why do high concentrations of salt induce a negative valence only when the need for salt is low?” A better understanding of regulation of salt homeostasis could improve our understanding of why our brains enjoy salty food so much.

Induction apoptosis in liver cancer cells by altering natural hydroxyapatite to scavenge excess sodium without deactivate sodium-potassium pump

Many studies point to the important role of sodium and potassium in many pathways, like cellular differentiation, division, homeostasis, electrolyte balances, pH regulation, nerve impulses, and apoptosis. Cancer cells keep more sodium in their cytoplasm compared to the normal cell, which may reveal that Na+ has a vital role in cancer cell homeostasis and their frequent division. Therefore, the ability of natural-based hydroxyapatite (HAp) to scavenging sodium from the cytoplasm will disrupt the internal homeostasis leading to activate apoptosis pathways. Where each hydroxyapatite molecule can scavenge three molecules of sodium but not potassium, this is due to the nuclear size difference between sodium and potassium. Accordingly, this study designed in hope to induce apoptosis by disruption of cellular homeostasis by scavenging internal sodium using natural-based hydroxyapatite (HAp). On the other hand, the passage of (HAp) composite across cell membrane facilitated by doping with lithium. Li doped to natural hydroxyapatite (Li-HAp) using wet impregnation method. The prepared sample characterized utilizing a scanning electron microscope (SEM), x-ray diffraction (XRD), Fourier transform infrared (FTIR) and Raman spectroscopy techniques. The response of HepG2 against HAp doped with 0.1% Li investigated. Results showed that the rate of apoptosis observed in treated liver cancer cells (HepG2), has increased as sodium decreased. Where, the internal sodium concentration reduced by one-third, while potassium concentration increased by one-sixth comparing to treated cells with HAp alone as Li alone. Therefore, the induction of apoptosis presented a significant raise when cells treated with Li-HAp. In the light of these observations, Li-HAp may have good chance to be not only the anticancer candidate drug but also can use in the regulation of some muscle contraction, nerve impulses and hypertension diseases as a candidate drug.

Phytotoxicity of glyphosate in the germination of Pisum sativum and its effect on germinated seedlings.

The present study evaluated the effects of glyphosate on Pisum sativum germination as well as its effect on the physiology and biochemistry of germinated seedlings. Different physico-chemical biomarkers, viz., chlorophyll, root and shoot length, total protein and soluble sugar, along with sodium and potassium concentration, were investigated in germinated seedlings at different glyphosate concentrations. This study reports the influence of different concentrations of glyphosate on pea seeds and seedlings. Physicochemical biomarkers were significantly changed by glyphosate exposure after 15 days. The germination of seedlings under control conditions (0 mg/L) was 100% after 3 days of treatment but at 3 and 4 mg/L glyphosate, germination was reduced to 55 and 40%, respectively. Physiological parameters like root and shoot length decreased monotonically with increasing glyphosate concentration, at 14 days of observation. Average root and shoot length (n=30 in three replicates) were reduced to 14.7 and 17.6%, respectively, at 4 mg/L glyphosate. Leaf chlorophyll content also decreased, with a similar trend to root and shoot length, but the protein content initially decreased and then increased with an increase in glyphosate concentration to 3 mg/L. The study suggests that glyphosate reduces the soluble sugar content significantly, by 21.6% (v/v). But internal sodium and potassium tissue concentrations were significantly altered by glyphosate exposure with increasing concentrations of glyphosate. Biochemical and physiological analysis also supports the inhibitory effect of glyphosate on seed germination and biochemical effects on seedlings.

Ionic regulation in the Antarctic nematode Panagrolaimus davidi, measured using electron probe X-ray microanalysis

The element composition of the pseudocoelomic fluid of the Antarctic nematode Panagrolaimus davidi was analysed by electron probe X-ray microanalysis after absorbing the fluid into Sephadex G-25 beads, and after producing calibration curves by analysing various concentrations of elements of interest absorbed into beads. The nematodes maintain higher concentrations of sodium and potassium in their pseudocoelomic fluid than in the external medium but lower concentrations of magnesium and calcium. When external concentrations of specific ions were elevated there was evidence for the regulation of internal concentrations of sodium, potassium, magnesium and chlorine. The time course of changes in response to exposure to elevated levels of KCl shows an increase in internal concentrations of potassium and chlorine up to 2h after exposure, followed by a decline. This is consistent with a model of ionic regulation proposed for Caenorhabditis elegans which suggests that high concentrations of ionic osmolytes are replaced by compatible organic osmolytes.

A kinetic model for sodium transport via a non‐gastric H+(Na+)/K+ ATPase

Experimental results have suggested that macula densa (MD) cells have a unique way of regulating cellular sodium concentration via an apical H+(Na+)/K+‐ATPase. We developed a kinetic model to represent the sodium transport via this transporter. The model assumes a 2:2 stoichiometry for both the hydrogen and sodium cycles. Rate constant values for the hydrogen cycle were obtained from a renal H+/K+‐ATPase model (A.M. Weinstein, Am J Physiol Renal Physiol 274:F856‐F867, 1998) which were, in turn, based on values obtained from a gastric H+/K+‐ATPase model (P. Brzezinski et al., Biochim. Biophys. Acta 942:215–219, 1988). Rate constants for the sodium cycle are assumed to be equal to those in the hydrogen cycle. Results showed that sodium extrusion is very sensitive to changes in luminal potassium concentration from 0 to 20 mM. In addition, sodium extrusion as a function of internal sodium concentration saturates at ~70 mM. This ATPase pump model is essential in the development of larger scale models of ion transport by the MD cells.Research supported by MBRS‐RISE grant 2R25GM061151‐09 and by NIH‐NIGMS grant SC1GM084744.

Growth and Physiological Responses of Landscape Plants to Saline Water Irrigation: A Review

Water shortages and poor water quality are critical issues in many areas of the world. With rapid increases in population and shortage of water supplies in urban areas, use of alternative water sources such as municipal reclaimed water and other sources of non-potable waters for irrigating landscapes is inevitable. A potential concern is the elevated salt levels in these alternative waters. This article briefly summarizes general information regarding alternative water sources and general responses of landscape plants to salinity stress. Methodology of screening and evaluating salt tolerance of landscape plants are discussed. Recent research results on salt tolerance of landscape plants and their physiological responses to salinity stress are reviewed. Like agricultural crops, a wide range of salt tolerance among landscape plants has been found. In addition to plant species, dominant salt type, substrate, irrigation method and management, and environmental conditions also affect plant responses to salinity stress. A number of mechanisms of salinity tolerance have been observed among landscape species, including restriction of ion uptake, selective ion uptake, and tolerance to high internal concentrations of sodium and/or chloride.

Ionic conditions modulate stimulus-induced capacitance changes in isolated neurohypophysial terminals of the rat

Peptidergic nerve terminals of the neurohypophysis (NH) secrete both oxytocin and vasopressin upon stimulation with peptide-specific bursts of action potentials from magnocellular neurons. These bursts vary in both frequency and action potential duration and also induce in situ ionic changes both inside and outside the terminals in the NH. These temporary effects include the increase of external potassium and decrease of external calcium, as well as the increase in internal sodium and chloride concentrations. In order to determine any mechanism of action that these ionic changes might have on secretion, stimulus-induced capacitance recordings were performed on isolated terminals of the NH using action potential burst patterns of varying frequency and action potential width. The results indicate that in NH terminals: (1) increased internal chloride concentration improves the efficiency of action potential-induced capacitance changes, (2) increasing external potassium increases stimulus-induced capacitance changes, (3) decreasing external calcium decreases the capacitance induced by low frequency broadened action potentials, while no capacitance change is observed with high frequency un-broadened action potentials, and (4) increasing internal sodium increases the capacitance change induced by low frequency bursts of broadened action potentials, more than for high frequency bursts of narrow action potentials. These results are consistent with previous models of stimulus-induced secretion, where optimal secretory efficacy is determined by particular characteristics of action potentials within a burst. Our results suggest that positive effects of increased internal sodium and external potassium during a burst may serve as a compensatory mechanism for secretion, counterbalancing the negative effects of reduced external calcium. In this view, high frequency un-broadened action potentials (initial burst phase) would condition the terminals by increasing internal sodium for optimal secretion by the physiological later phase of broadened action potentials. Thus, ionic changes occurring during a burst may help to make such stimulation more efficient at inducing secretion. Furthermore, these effects are thought to occur within the initial few seconds of incoming burst activity at both oxytocin and vasopressin types of NH nerve terminals.

Effect of aldosterone on kinetics of intracellular sodium in cortical portion of collecting ducts in rat kidney

We studied the effect of protein kinase C inhibitor RO-31-8220 (10(-7) M) on rapid nongenomic effect of aldosterone in cells of isolated segment of distal region of collecting duct in rat kidney. Experiments with fluorescent dye Na-Green showed that the inhibitor abolished the modulating effect of aldosterone (10 nM) on intracellular sodium concentration at external sodium concentration of 14 mM. Aldosterone decreased by half the initial rate of the changes in internal sodium concentration in both 10-day and mature rats (p<0.05). Similarly to sodium channel blocker amiloride (10(-5) M), RO-31-8220 abolished rapid nongenomic effect of aldosterone on the rate of the changes in internal sodium concentration.

The effect of extreme waterborne cadmium exposure on the internal concentrations of cadmium, calcium, and sodium in Chironomus riparius larvae

Chironomus riparius larvae (3rd–4th instar) were extremely resistant to waterborne Cd with 48 h LC50s of 331 mg Cd/L in soft water (10 mg/L CaCO 3) and 1106 mg Cd/L in moderately hard (140 mg CaCO 3/L) water. Unexposed larvae had whole body Ca and Na concentrations of 11.2(0.3) and 84.5(3.0) μmol/g, respectively. The larvae exposed through acute toxicity tests accumulated massive amounts of Cd, reaching >50 μmol/g in larvae exposed to 437 mg Cd/L, though burdens were lower at higher exposure concentrations. These Cd burdens were approximately fivefold greater than whole-body Ca concentrations. Cd exposure also had a significant negative effect on internal Ca: whole-body Ca declined by over 70% in larvae exposed to Cd above the LC50 concentration. The effect of Cd exposure on whole-body Na was much less dramatic as levels dropped by 10–28% in the acutely exposed larvae. Time series exposures (up to 72 h) across a range of Cd concentrations (0.1–865 mg/L) revealed that internal Ca dropped within the first hour of exposure regardless of the concentration of Cd. In all but the highest (865 mg Cd/L) exposure, internal Ca eventually recovered to the control level. Cd resistance in C. riparius may lie in its ability to maintain internal Ca balance even when exposed to extreme (>100 mg/L) levels of Cd, coupled with remarkable capacities for storage–detoxification and excretion of Cd.

Fluorescence Measurement of Intracellular Sodium Concentration in Single Escherichia coli Cells

The energy-transducing cytoplasmic membrane of bacteria contains pumps and antiports maintaining the membrane potential and ion gradients. We have developed a method for rapid, single-cell measurement of the internal sodium concentration ([Na +] in) in Escherichia coli using the sodium ion fluorescence indicator, Sodium Green. The bacterial flagellar motor is a molecular machine that couples the transmembrane flow of ions, either protons (H +) or sodium ions (Na +), to flagellar rotation. We used an E. coli strain containing a chimeric flagellar motor with H +- and Na +-driven components that functions as a sodium motor. Changing external sodium concentration ([Na +] ex) in the range 1–85 mM resulted in changes in [Na +] in between 5–14 mM, indicating a partial homeostasis of internal sodium concentration. There were significant intercell variations in the relationship between [Na +] in and [Na +] ex, and the internal sodium concentration in cells not expressing chimeric flagellar motors was 2–3 times lower, indicating that the sodium flux through these motors is a significant fraction of the total sodium flux into the cell.

Dietary sodium inhibits aqueous copper uptake in rainbow trout(Oncorhynchus mykiss)

Ours is the first study to demonstrate an influence of dietary sodium on waterborne copper uptake in fish. We examined possible interactions between dietary sodium and the response of freshwater rainbow trout (Oncorhynchus mykiss) to waterborne copper in light of recent evidence of interactions between sodium and copper metabolism in the gills. Trout were maintained for 6 days on one of four diets of increasing sodium concentration (0.25 mmol g(-1), 0.51 mmol g(-1), 0.76 mmol g(-1) and 1.27 mmol g(-1), which corresponds to 0.6%, 1.2%, 1.8% and 3% sodium by mass, respectively). At the end of 7 days, fish were exposed for 6 h to waterborne copper spiked with (64)Cu to determine if the dietary sodium affected responses to a subsequent short-term waterborne copper exposure. The radiotracer allowed us to distinguish between Cu occurring in fish tissues before the experiment and 'newly accumulated' Cu arising from the experimental exposure. Dietary sodium concentrations of 1.8% or 3% reduced newly accumulated copper concentrations in gill (from 93.9 ng g(-1) in control to 38.9 ng g(-1) and 20.0 ng g(-1) in fish fed 1.8% or 3% Na(+)-supplemented diets, respectively), liver (from 64.3 ng g(-1) to 23.1 ng g(-1) and 7.5 ng g(-1), respectively), kidney (from 29.3 ng g(-1) to 11.7 ng g(-1) and 7.8 ng g(-1), respectively), plasma (from 64.7 ng g(-1) to 21.5 ng g(-1) and 10.7 ng g(-1), respectively) and gut (from 6.8 ng g(-1) to 3.4 ng g(-1) and 2.2 ng g(-1), respectively) by 50.0-88.2%. The 3% Na(+)-supplemented diets also increased plasma and gut sodium concentrations by 38.1% (from 137.1 micromol g(-1) to 189.3 micromol g(-1)) and 104.3% (from 56.5 micromol g(-1) to 115.4 micromol g(-1)), respectively, relative to fish maintained on untreated diets. Whole body uptake rates of both sodium and copper were significantly reduced, and highly correlated (r=0.97) with one another, in fish fed high-sodium diets relative to controls. Moreover, sodium efflux was 12% and 38% higher in fish fed 1.8% and 3% sodium-enriched diets, respectively. Fish fed high-sodium diets also drank more water, but the contribution of drinking to waterborne copper uptake was negligible. From these results, we speculate that, at least in part, aqueous sodium and copper share a common branchial uptake route, probably through an apical sodium channel. According to this hypothesis, as the channel is downregulated with increasing internal sodium concentrations, both sodium and copper uptake from the water are inhibited.

Molecular Mechanism of the ATP Synthase's F o Motor Probed by Mutational Analyses of Subunit a

The most prominent residue of subunit a of the F 1F o ATP synthase is a universally conserved arginine (aR227 in Propionigenium modestum), which was reported to permit no substitution with retention of ATP synthesis or H +-coupled ATP hydrolysis activity. We show here that ATP synthases with R227K or R227H mutations in the P. modestum a subunit catalyse ATP-driven Na + transport above or below pH 8.0, respectively. Reconstituted F o with either mutation catalysed 22Na + out/Na + in exchange with similar pH profiles as found in ATP-driven Na + transport. ATP synthase with an aR227A substitution catalysed Na +-dependent ATP hydrolysis, which was completely inhibited by dicyclohexylcarbodiimide, but not coupled to Na + transport. This suggests that in the mutant the dissociation of Na + becomes more difficult and that the alkali ions remain therefore permanently bound to the c subunit sites. The reconstituted mutant enzyme was also able to synthesise ATP in the presence of a membrane potential, which stopped at elevated external Na + concentrations. These observations reinforce the importance of aR227 to facilitate the dissociation of Na + from approaching rotor sites. This task of aR227 was corroborated by other results with the aR227A mutant: (i) after reconstitution into liposomes, F o with the aR227A mutation did not catalyse 22Na + out/Na + in exchange at high internal sodium concentrations, and (ii) at a constant ΔpNa +, 22Na + uptake was inhibited at elevated internal Na + concentrations. Hence, in mutant aR227A, sodium ions can only dissociate from their rotor sites into a reservoir of low sodium ion concentration, whereas in the wild-type the positively charged aR227 allows the dissociation of Na + even into compartments of high Na + concentration.

Changes in cell volume and internal sodium concentration in HeLa cells during exponential growth and following lonidamine treatment

Cell volumes decreased in HeLa cells as a function of time after seeding during exponential growth. Cell volume distributions revealed the presence of two cell populations in all stages of growth. When cells approached confluence, the ratio of the two populations abruptly shifted towards that characterised by the smallest volume. Percentages of G1-, S- and G2 + M-phase cells were also measured and it was found that G1 frequency increased as a function of cell density during exponential growth. Intracellular sodium concentration, [Na]i was monitored by 23Na NMR in the presence of 5 mM dysprosium (III) tripolyphosphate. [Na]i increased from 22.8 to 59.0 mM in cells from the second to the seventh day after seeding. Treatment with lonidamine, an antitumoral drug that it is known to slow down cell growth by affecting aerobic glycolysis, produced a complete block of cell progression after a few days of treatment. The progression of cell volume distributions towards smaller volumes and the increase in internal sodium concentration as a function of time after seeding were also affected by the drug. These phenomena were related to the existence of a subpopulation of mitotically inactive G1-phase cells during exponential growth, pointing out that a density-dependent cellular mechanism regulates the cell cycling in HeLa cells.

The inorganic ion content of native aquatic bacteria

In this study we have quantified the ionic content and volume of native aquatic, and two cultured bacteria, by X-ray microanalysis (XRMA) in the transmission electron microscope (TEM). The cellular concentrations of magnesium (means of 630 and 710 mM) were more than an order of a magnitude higher than the outside concentrations. The internal concentrations of sodium were on average 50-180 mM, and the [K+]/[Na+] ratios were in the range of 0.1-0.5; lowest for apparently nonactive bacteria. Magnesium and chloride probably act as the major components of cell turgor, since no other inorganic ions were present in comparable amounts. Our carbon and nitrogen measurements indicated that organic solutes are not likely to be present at significant concentrations. The estimated charge of inorganic ions (Na, Mg, P, Cl, K, and Ca) gave a positive net internal charge for most cells. However, in cultures of Vibrio natriegens, the high internal chloride concentration made the net inorganic charge negative in these cells. Our results suggest that growing marine bacterioplankton have an internal environment in which magnesium is the dominating cation. These results suggest that actively growing marine bacteria are physiologically adapted to high internal concentrations of both magnesium and chloride.

Alpha- and beta-scorpion toxins evoke glutamate release from rat cortical synaptosomes with different effects on [Na +] i and [Ca 2+] i

Scorpion toxins have long been used as tools in the investigation of neurotransmitter release mechanisms. We have used rat cortical synaptosomes to study the effects of a β-type scorpion toxin (TiTX- γ) on the release of glutamate and on the concentrations of free sodium and calcium ions inside the synaptosomes. The effects are compared with those of an α-type scorpion toxin (TsTX), on which there have been more studies. TsTX increased overall internal sodium and calcium ion concentrations and glutamate release in an incremental, dose dependent manner. TiTX- γ similarly evoked glutamate release in an incremental, dose dependent manner. However, TiTX- γ caused little increase in the overall internal sodium and calcium ion concentrations at low doses that evoked a significant release of glutamate and a maximal increase in these ions at somewhat higher doses. The results suggest that TiTX- γ preferentially binds sodium channels close to the active zones for glutamate release and indicates that modifications of the activation or inactivation of the Na +-channel can lead to very different changes in the cytosolic concentrations of free Na +and Ca 2+, with consequences for neurotransmission. This provides an interesting perspective concerning modulation of neurotransmitter release via pharmacological manipulation of Na +-channel properties, that may lead to a better comprehension of its physiological and pathological roles.

Summary of Studies of Changes in Vascular Reactivity Caused by Natriuretic Hormones

Endogenous Na, K pumpinhibitors may contribute to the pathogenesis of hypertension, and could do so by causing direct vasoconstriction and/or enhancing sensitivity to other vasoconstrictor agents. These effects of the Na, K pump inhibitors are likely due to inhibition of Na-K-ATPase. In turn, cells become depolarized, internal sodium concentration increases and internal calcium is increased by exchange for sodium via the sodium/calcium exchange carrier. This extra calcium is sequestered, increasing the size of the releasable intracellular calcium pool. Both depolarization and the increase in cytosolic calcium can cause vasoconstriction. Both depolarization and the increased size the intracellular calcium pool can sensitize the blood vessel to other vasoconstrictor agents. Endogenous pump inhibitors may also stimulate the release of catecholamines from the intramural sympathetic nerve terminals. Studies of a variety of candidate endogenous Na, K pumpinhibitors are reviewed. These include presently unidentified substances extracted from human urine, from peritoneal dialysate of hypertensives with renal failure, and from bovine and rat hypothalamus. Additional candidate compounds include ouabain, selected pregnanes and marinobufagenin, a steroid originally identified in the venom of the frog, Bufo marinus

Editorial: Sodium-hydrogen exchange inhibition—superior cardioprotective strategy

Editorial: Sodium-hydrogen exchange inhibition—superior cardioprotective strategy

A method for screening rice plants for salt tolerance

A number of varieties of rice, a halophyte, Sesuvium portulacastrum and a glycophyte, Phaseolus vulgaris were grown in culture solution containing a range of concentrations of NaCl. Growth of the plants and internal sodium concentrations of the roots were measured after 14 days. The electrical potential difference (PD) between the external solution and the vacuole of the outer cells of the root was also measured. This enabled the driving force on sodium at the cell membranes to be calculated using the Nernst equation. It was found that Sesuvium and those varieties of rice that had previously shown salt tolerance generated relatively negative PDs and large driving forces tending to exclude sodium from the root. This suggested that a simple measurement of PD for plants grown in a given concentration of NaCl over a given period of time would provide a fairly rapid screening method for salt tolerance in rice and possibly other species also. T J Flowers Section editor

Dynamics of Abnormal Pacemaking Activity in Cardiac Purkinje Fibers

A model of the electrical activity in mammalian cardiac Purkinje fiber is examined to study the effects of subcellular oscillations on the transmembrane potential. Inhibition of the sodium/potassium pump causes oscillations in the internal calcium concentration and these oscillations are shown to interfere with the normal pacemaking mechanism of the Purkinje fiber. Bifurcation diagrams were constructed using numerical continuation methods. These results predict a dramatic change in the structure of periodic orbits of the cell electrical activity with pump inhibition and elevated levels of internal sodium concentration.

Selection of a lysine-resistant CHO-K1 mutant with reduced amino acid transport through multiple systems

High levels of L-lysine were used to select for resistant variants of Chinese hamster ovary (CHO-K1) cells. Surviving colonies were screened for altered lysine transport and two with reduced uptake were picked. Clone CH-Kr, derived from the more severely affected colony, was analyzed in detail. In starved cells the Vmax of lysine uptake in CH-Kr was half that of CHO while Km was unaltered. The intracellular pool of lysine, a substrate of cationic amino acid transport system y+, was significantly lower in CH-Kr. However, transport and pools of other amino acids, which are not substrates of y+, were also reduced in CH-Kr, as was the internal sodium concentration, while hexose import was increased. It appears that the mutation in CH-Kr is pleiotropic, affecting some general aspects of amino acid transport.