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American Journal of Physiology. Renal... Sep 2023The urinary potassium (K) excretion machinery is upregulated with increasing dietary K, but the role of accompanying dietary anions remains inadequately characterized....
The urinary potassium (K) excretion machinery is upregulated with increasing dietary K, but the role of accompanying dietary anions remains inadequately characterized. Poorly absorbable anions, including [Formula: see text], are thought to increase K secretion through a transepithelial voltage effect. Here, we tested if they also influence the K secretion machinery. Wild-type mice, aldosterone synthase (AS) knockout (KO) mice, or pendrin KO mice were randomized to control, high-KCl, or high-KHCO diets. The K secretory capacity was assessed in balance experiments. Protein abundance, modification, and localization of K-secretory transporters were evaluated by Western blot analysis and confocal microscopy. Feeding the high-KHCO diet increased urinary K excretion and the transtubular K gradient significantly more than the high-KCl diet, coincident with more pronounced upregulation of epithelial Na+ channels (ENaC) and renal outer medullary K (ROMK) channels and apical localization in the distal nephron. Experiments in AS KO mice revealed that the enhanced effects of [Formula: see text] were aldosterone independent. The high-KHCO diet also uniquely increased the large-conductance Ca-activated K (BK) channel β-subunit, stabilizing BKα on the apical membrane, the Cl/[Formula: see text] exchanger, pendrin, and the apical KCl cotransporter (KCC3a), all of which are expressed specifically in pendrin-positive intercalated cells. Experiments in pendrin KO mice revealed that pendrin was required to increase K excretion with the high-KHCO diet. In summary, [Formula: see text] stimulates K excretion beyond a poorly absorbable anion effect, upregulating ENaC and ROMK in principal cells and BK, pendrin, and KCC3a in pendrin-positive intercalated cells. The adaptive mechanism prevents hyperkalemia and alkalosis with the consumption of alkaline ash-rich diets but may drive K wasting and hypokalemia in alkalosis. Dietary anions profoundly impact K homeostasis. Here, we found that a K-rich diet, containing [Formula: see text] as the counteranion, enhances the electrogenic K excretory machinery, epithelial Na channels, and renal outer medullary K channels, much more than a high-KCl diet. It also uniquely induces KCC3a and pendrin, in B-intercalated cells, providing an electroneutral KHCO secretion pathway. These findings reveal new K balance mechanisms that drive adaption to alkaline and K-rich foods, which should guide new treatment strategies for K disorders.
Topics: Animals; Mice; Alkalosis; Anion Transport Proteins; Anions; Diet; Mice, Knockout; Potassium; Potassium, Dietary; Sodium; Sulfate Transporters
PubMed: 37498547
DOI: 10.1152/ajprenal.00193.2023 -
International Journal of Molecular... Nov 2023Ternary glassy electrolytes containing KS as a glass modifier and PS as a network former are synthesized by introducing a new type of complex and asymmetric salt,...
Ternary glassy electrolytes containing KS as a glass modifier and PS as a network former are synthesized by introducing a new type of complex and asymmetric salt, potassium triflate (KOTf), to obtain unprecedented K ion conductivity at ambient temperature. The glasses are synthesized using a conventional quenching technique at a low temperature. In general, alkali ionic glassy electrolytes of ternary systems, specifically for Li and Na ion conductivity, have been studied with the addition of halide salts or oxysalts such as MSO, MSiO, MPO (M = Li or Na), etc. We introduce a distinct and complex salt, potassium triflate (KOTf) with asymmetric anion, to the conventional glass modifier and former to synthesize K-ion-conducting glassy electrolytes. Two series of glassy electrolytes with a ternary system of (0.9-x)KS-xPS-0.1KOTf (x = 0.15, 0.30, 0.45, 0.60, and 0.75) and z(KS-2PS)-yKOTf (y = 0.05, 0.10, 0.15, 0.20, and 0.25) on a straight line of z(KS-2PS) are studied for their K ionic conductivities by using electrochemical impedance spectroscopy (EIS). The composition 0.3KS-0.6PS-0.1KOTf is found to have the highest conductivity among the studied glassy electrolytes at ambient temperature with the value of 1.06 × 10 S cm, which is the highest of all pure K-ion-conducting glasses reported to date. Since the glass transition temperatures of the glasses are near 100 °C, as demonstrated by DSC, temperature-dependent conductivities are studied within the range of 25 to 100 °C to determine the activation energies. A Raman spectroscopic study shows the variation in the structural units PS43-, P2S74-, and P2S64- of the network former for different glassy electrolytes. It seems that there is a role of P2S74- and P2S64- in K-ion conductivity in the glassy electrolytes because the spectroscopic results are compatible with the composition-dependent, room-temperature conductivity trend.
Topics: Electrolytes; Ions; Phosphates; Potassium; Sodium Chloride; Sodium Chloride, Dietary
PubMed: 38069182
DOI: 10.3390/ijms242316855 -
Pflugers Archiv : European Journal of... Mar 2015Dietary potassium (K(+)) intake has antihypertensive effects, prevents strokes, and improves cardiovascular outcomes. The underlying mechanism for these beneficial... (Review)
Review
Dietary potassium (K(+)) intake has antihypertensive effects, prevents strokes, and improves cardiovascular outcomes. The underlying mechanism for these beneficial effects of high K(+) diets may include vasodilation, enhanced urine flow, reduced renal renin release, and negative sodium (Na(+)) balance. Indeed, several studies demonstrate that dietary K(+) intake induces renal Na(+) loss despite elevated plasma aldosterone. This review briefly highlights the epidemiological and experimental evidences for the effects of dietary K(+) on arterial blood pressure. It discusses the pivotal role of the renal distal tubule for the regulation of urinary K(+) and Na(+) excretion and blood pressure and highlights that it depends on the coordinated interaction of different nephron portions, epithelial cell types, and various ion channels, transporters, and ATPases. Moreover, we discuss the relevance of aldosterone and aldosterone-independent factors in mediating the effects of an altered K(+) intake on renal K(+) and Na(+) handling. Particular focus is given to findings suggesting that an aldosterone-independent downregulation of the thiazide-sensitive NaCl cotransporter significantly contributes to the natriuretic and antihypertensive effect of a K(+)-rich diet. Last but not least, we refer to the complex signaling pathways enabling the kidney to adapt its function to the homeostatic needs in response to an altered K(+) intake. Future work will have to further address the underlying cellular and molecular mechanism and to elucidate, among others, how an altered dietary K(+) intake is sensed and how this signal is transmitted to the different epithelial cells lining the distal tubule.
Topics: Animals; Blood Pressure; Humans; Kidney; Potassium, Dietary; Renal Reabsorption; Water-Electrolyte Balance
PubMed: 25559844
DOI: 10.1007/s00424-014-1673-1 -
Current Opinion in Nephrology and... Jul 2019This review focuses on the role of intracellular chloride in regulating transepithelial ion transport in the distal convoluted tubule (DCT) in response to perturbations... (Review)
Review
PURPOSE OF REVIEW
This review focuses on the role of intracellular chloride in regulating transepithelial ion transport in the distal convoluted tubule (DCT) in response to perturbations in plasma potassium homeostasis.
RECENT FINDINGS
Low dietary potassium increases the phosphorylation and activity of the sodium chloride cotransporter (NCC) in the DCT, and vice versa, affecting sodium-dependent potassium secretion in the downstream aldosterone-sensitive distal nephron. In cells, NCC phosphorylation is increased by lowering of intracellular chloride, via activation of the chloride-sensitive with no lysine (WNK)-SPAK/OSR1 (Ste20-related proline/alanine-rich kinase/oxidative stress response) kinase cascade. In-vivo studies have demonstrated pathway activation in the kidney in response to low dietary potassium. A possible mechanism is lowering of DCT intracellular chloride in response to low potassium because of parallel basolateral potassium and chloride channels. Recent studies support a role for these channels in the response of NCC to varying potassium. Studies examining chloride-insensitive WNK mutants, in the Drosophila renal tubule and in the mouse, lend further support to a role for chloride in regulating WNK activity and transepithelial ion transport. Caveats, alternatives, and future directions are also discussed.
SUMMARY
Chloride sensing by WNK kinase provides a mechanism to allow coupling of extracellular potassium with NCC phosphorylation and activity to maintain potassium homeostasis.
Topics: Animals; Biological Transport; Chlorides; Homeostasis; Humans; Kidney Tubules, Distal; Mice; Nephrons; Phosphorylation; Potassium; Sodium Chloride Symporters
PubMed: 30865168
DOI: 10.1097/MNH.0000000000000502 -
The British Journal of Nutrition Mar 2006
Review
Topics: Adult; Animals; Bone Density; Calcium; Calcium Sulfate; Defecation; Diet; Female; Humans; Intestinal Absorption; Milk; Mineral Waters; Potassium, Dietary
PubMed: 16512952
DOI: 10.1079/bjn20051652 -
Gastroenterology Aug 1994When normal people ingest 90 mEq/day of K+ in their diet, they absorb about 90% of intake (81 mEq) and excrete an equivalent amount of K+ in the urine. Normal fecal K+... (Review)
Review
When normal people ingest 90 mEq/day of K+ in their diet, they absorb about 90% of intake (81 mEq) and excrete an equivalent amount of K+ in the urine. Normal fecal K+ excretion averages about 9 mEq/day. The vast majority of intestinal K+ absorption occurs in the small intestine; the contribution of the normal colon to net K+ absorption and secretion is trivial. K+ is absorbed or secreted mainly by passive mechanisms; the rectum and perhaps the sigmoid colon have the capacity to actively secrete K+, but the quantitative and physiological significance of this active secretion is uncertain. Hyperaldosteronism increases fecal K+ excretion by about 3 mEq/day in people with otherwise normal intestinal tracts. Cation exchange resin by mouth can increase fecal K+ excretion to 40 mEq/day. The absorptive mechanisms of K+ are not disturbed by diarrhea per se, but fecal K+ losses are increased in diarrheal diseases by unabsorbed anions (which obligate K+), by electrochemical gradients secondary to active chloride secretion, and probably by secondary hyperaldosteronism. In diarrhea, total body K+ can be reduced by two mechanisms: loss of muscle mass because of malnutrition and reduced net absorption of K+; only the latter causes hypokalemia. Balance studies in patients with diarrhea are exceedingly rare, but available data emphasize an important role for dietary K+ intake, renal K+ excretion, and fecal K+ losses in determining whether or not a patient develops hypokalemia. The paradoxical negative K+ balance induced by ureterosigmoid anastomosis is described. The concept that fecal K+ excretion is markedly elevated in patients with uremia as an intestinal adaptation to prevent hyperkalemia is analyzed; we conclude that the data do not convincingly show the existence of a major intestinal adaptive response to chronic renal failure.
Topics: Adaptation, Physiological; Amiloride; Anastomosis, Surgical; Cation Exchange Resins; Colon; Diarrhea; Feces; Glucocorticoids; Humans; Hyperaldosteronism; Hypokalemia; Intestinal Absorption; Intestinal Mucosa; Intestine, Small; Intestines; Ion Transport; Kidney Failure, Chronic; Mineralocorticoids; Potassium; Potassium, Dietary; Ureter; Urinary Diversion
PubMed: 8039632
DOI: 10.1016/0016-5085(94)90184-8 -
American Journal of Veterinary Research Mar 2005To compare effects of oral supplementation with an experimental potassium-free sodium-abundant electrolyte mixture (EM-K) with that of oral supplementation with... (Comparative Study)
Comparative Study
OBJECTIVE
To compare effects of oral supplementation with an experimental potassium-free sodium-abundant electrolyte mixture (EM-K) with that of oral supplementation with commercial potassium-rich mixtures (EM+K) on acid-base status and plasma ion concentrations in horses during an 80-km endurance ride.
ANIMALS
46 healthy horses.
PROCEDURE
Blood samples were collected before the ride; at 21-, 37-, 56-, and 80-km inspection points; and during recovery (ie, 30-minute period after the ride). Consumed electrolytes were recorded. Blood was analyzed for pH, PvCO2, and Hct, and plasma was analyzed for Na+, K+, Cl-, Ca2+, Mg2+, lactate, albumin, phosphate, and total protein concentrations. Plasma concentrations of H+ and HCO3-, the strong ion difference (SID), and osmolarity were calculated.
RESULTS
34 (17 EM-K and 17 EM+K treated) horses finished the ride. Potassium intake was 33 g less and Na+ intake was 36 g greater for EM-K-treated horses, compared with EM+K-treated horses. With increasing distance, plasma osmolarity; H+, Na+, K+, Mg2+, phosphate, lactate, total protein, and albumin concentrations; and PvCO2 and Hct were increased in all horses. Plasma HCO3-, Ca2+, and Cl- concentrations were decreased. Plasma H+ concentration was significantly lower in EM-K-treated horses, compared with EM+K-treated horses. Plasma K+ concentrations at the 80-km inspection point and during recovery were significantly less in EM-K-treated horses, compared with EM+K-treated horses.
CONCLUSIONS AND CLINICAL RELEVANCE
Increases in plasma H+ and K+ concentrations in this endurance ride were moderate and unlikely to contribute to signs of muscle fatigue and hyperexcitability in horses.
Topics: Acid-Base Equilibrium; Analysis of Variance; Animals; Blood Chemical Analysis; Electrolytes; Horses; Hydrogen-Ion Concentration; Ions; Muscle, Skeletal; Osmolar Concentration; Physical Exertion; Potassium, Dietary
PubMed: 15822592
DOI: 10.2460/ajvr.2005.66.466 -
The Journal of Nutrition Nov 2004Potassium (K+) requirements have been largely overlooked because severe deficiencies are uncommon due to the ubiquity of this element in foods. However, a transition... (Review)
Review
Potassium (K+) requirements have been largely overlooked because severe deficiencies are uncommon due to the ubiquity of this element in foods. However, a transition toward modern ("Westernized") diets has led to a substantial decline of K+ intake compared with traditional food habits, and a large fraction of the population might now have suboptimal K+ intake. A high K+ intake was demonstrated to have protective effects against several pathologic states affecting the cardiovascular system, kidneys, and bones. Additionally, fruits and vegetables contain K/organic anion salts (malate, citrate), which exert alkalinizing effects, through KHCO(3)(-) generation, which serves to neutralize fixed acidity in urine. Low-grade metabolic acidosis, when not properly controlled, may exacerbate various catabolic processes (bone Ca++ mobilization, proteolysis), especially in the elderly. Fruits and vegetables are therefore receiving great attention in a strategy to increase the nutritional value of meals while reducing energy density and intake. The need to ensure a 2.5- to 3.5-g daily K+ supply from fruits and vegetables represents a strong rationale for the "5-10 servings per day" recommendations.
Topics: Acid-Base Equilibrium; Blood Glucose; Bone Diseases; Cardiovascular Diseases; Cations, Divalent; Fruit; Humans; Hydrogen-Ion Concentration; Kidney Diseases; Nutritional Physiological Phenomena; Potassium, Dietary; Urine; Vegetables
PubMed: 15514249
DOI: 10.1093/jn/134.11.2903 -
American Journal of Physiology. Renal... Mar 2023The Cl/[Formula: see text] exchanger pendrin in the kidney maintains acid-base balance and intravascular volume. Pendrin is upregulated in models associated with high...
The Cl/[Formula: see text] exchanger pendrin in the kidney maintains acid-base balance and intravascular volume. Pendrin is upregulated in models associated with high circulating aldosterone concentration, such as dietary NaCl restriction or an aldosterone infusion. However, it has not been established if pendrin is similarly regulated by aldosterone with a high-K diet because the effects of accompanying anions have not been considered. Here, we explored how pendrin is modulated by different dietary potassium salts. Wild-type (WT) and aldosterone synthase (AS) knockout (KO) mice were randomized to control, high-KHCO, or high-KCl diets. Dietary KCl and KHCO loading increased aldosterone in WT mice to the same extent but had opposite effects on pendrin abundance. KHCO loading increased pendrin protein and transcript abundance. Conversely, high-KCl diet feeding caused pendrin to decrease within 8 h of switching from the high-KHCO diet, coincident with an increase in plasma Cl and a decrease in [Formula: see text]. In contrast, switching the high-KCl diet to the high-KHCO diet caused pendrin to increase in WT mice. Experiments in AS KO mice revealed that aldosterone is necessary to optimally upregulate pendrin protein in response to the high-KHCO diet but not to increase pendrin mRNA. We conclude that pendrin is differentially regulated by different dietary potassium salts and that its regulation is prioritized by the dietary anion, providing a mechanism to prevent metabolic alkalosis with high-K base diets and safeguard against hyperchloremic acidosis with consumption of high-KCl diets. Regulation of the Cl/[Formula: see text] exchanger pendrin has been suggested to explain the aldosterone paradox. A high-K diet has been proposed to downregulate a pendrin-mediated K-sparing NaCl reabsorption pathway to maximize urinary K excretion. Here, we challenged the hypothesis, revealing that the accompanying anion, not K, drives pendrin expression. Pendrin is downregulated with a high-KCl diet, preventing acidosis, and upregulated with an alkaline-rich high-K diet, preventing metabolic alkalosis. Pendrin regulation is prioritized for acid-base balance.
Topics: Animals; Mice; Acidosis; Aldosterone; Alkalosis; Anion Transport Proteins; Bicarbonates; Diet; Potassium; Potassium, Dietary; Salts; Sodium Chloride; Sulfate Transporters
PubMed: 36656986
DOI: 10.1152/ajprenal.00128.2022 -
Kidney International Jun 2017To maintain potassium homeostasis, kidneys exert flow-dependent potassium secretion to facilitate kaliuresis in response to elevated dietary potassium intake. This...
To maintain potassium homeostasis, kidneys exert flow-dependent potassium secretion to facilitate kaliuresis in response to elevated dietary potassium intake. This process involves stimulation of calcium-activated large conductance maxi-K (BK) channels in the distal nephron, namely the connecting tubule and the collecting duct. Recent evidence suggests that the TRPV4 channel is a critical determinant of flow-dependent intracellular calcium elevations in these segments of the renal tubule. Here, we demonstrate that elevated dietary potassium intake (five percent potassium) increases renal TRPV4 mRNA and protein levels in an aldosterone-dependent manner and causes redistribution of the channel to the apical plasma membrane in native collecting duct cells. This, in turn, leads to augmented TRPV4-mediated flow-dependent calcium ion responses in freshly isolated split-opened collecting ducts from mice fed the high potassium diet. Genetic TRPV4 ablation greatly diminished BK channel activity in collecting duct cells pointing to a reduced capacity to excrete potassium. Consistently, elevated potassium intake induced hyperkalemia in TRPV4 knockout mice due to deficient renal potassium excretion. Thus, regulation of TRPV4 activity in the distal nephron by dietary potassium is an indispensable component of whole body potassium balance.
Topics: Adaptation, Physiological; Animals; Calcium; Genetic Predisposition to Disease; Homeostasis; Hyperkalemia; Kidney Tubules; Large-Conductance Calcium-Activated Potassium Channels; Mice, Inbred C57BL; Mice, Knockout; Phenotype; Potassium, Dietary; Receptors, Mineralocorticoid; Renal Elimination; TRPV Cation Channels
PubMed: 28187982
DOI: 10.1016/j.kint.2016.12.010