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Nutrients Jul 2016Potassium is an essential nutrient. It is the most abundant cation in intracellular fluid where it plays a key role in maintaining cell function. The gradient of... (Review)
Review
Potassium is an essential nutrient. It is the most abundant cation in intracellular fluid where it plays a key role in maintaining cell function. The gradient of potassium across the cell membrane determines cellular membrane potential, which is maintained in large part by the ubiquitous ion channel the sodium-potassium (Na+-K+) ATPase pump. Approximately 90% of potassium consumed (60-100 mEq) is lost in the urine, with the other 10% excreted in the stool, and a very small amount lost in sweat. Little is known about the bioavailability of potassium, especially from dietary sources. Less is understood on how bioavailability may affect health outcomes. Hypertension (HTN) is the leading cause of cardiovascular disease (CVD) and a major financial burden ($50.6 billion) to the US public health system, and has a significant impact on all-cause morbidity and mortality worldwide. The relationship between increased potassium supplementation and a decrease in HTN is relatively well understood, but the effect of increased potassium intake from dietary sources on blood pressure overall is less clear. In addition, treatment options for hypertensive individuals (e.g., thiazide diuretics) may further compound chronic disease risk via impairments in potassium utilization and glucose control. Understanding potassium bioavailability from various sources may help to reveal how specific compounds and tissues influence potassium movement, and further the understanding of its role in health.
Topics: Cardiovascular Diseases; Diabetes Mellitus, Type 2; Dietary Supplements; Evidence-Based Medicine; Global Health; Glucose Intolerance; Humans; Hypertension; Intestinal Absorption; Kidney; Models, Biological; Potassium; Potassium Deficiency; Potassium, Dietary; Renal Elimination; Renal Reabsorption
PubMed: 27455317
DOI: 10.3390/nu8070444 -
Pediatric Nephrology (Berlin, Germany) Jul 2017The kidney plays an essential role in maintaining homeostasis of ion concentrations in the blood. Because the concentration gradient of potassium across the cell... (Review)
Review
The kidney plays an essential role in maintaining homeostasis of ion concentrations in the blood. Because the concentration gradient of potassium across the cell membrane is a key determinant of the membrane potential of cells, even small deviations in serum potassium level from the normal setpoint can lead to severe muscle dysfunction, resulting in respiratory failure and cardiac arrest. Less severe hypo- and hyperkalemia are also associated with morbidity and mortality across various patient populations. In addition, deficiencies in potassium intake have been associated with hypertension and adverse cardiovascular and renal outcomes, likely due in part to the interrelated handling of sodium and potassium by the kidney. Here, data on the beneficial effects of potassium on blood pressure and cardiovascular and renal outcomes will be reviewed, along with the physiological basis for these effects. In some patient populations, however, potassium excess is deleterious. Risk factors for the development of hyperkalemia will be reviewed, as well as the risks and benefits of existing and emerging therapies for hyperkalemia.
Topics: Aldosterone; Cation Exchange Resins; Cell Membrane; Child; Heart Failure; Homeostasis; Humans; Hyperkalemia; Hypertension; Hypokalemia; Kidney; Membrane Potentials; Polymers; Potassium; Potassium, Dietary; Protein Serine-Threonine Kinases; Recommended Dietary Allowances; Renal Elimination; Renin-Angiotensin System; Respiratory Insufficiency; Risk Factors; Signal Transduction; Silicates; Sodium; Sodium Chloride Symporters; WNK Lysine-Deficient Protein Kinase 1
PubMed: 27194424
DOI: 10.1007/s00467-016-3411-8 -
Nature Communications May 2023Excitatory amino acid transporters (EAATs) uptake glutamate into glial cells and neurons. EAATs achieve million-fold transmitter gradients by symporting it with three...
Excitatory amino acid transporters (EAATs) uptake glutamate into glial cells and neurons. EAATs achieve million-fold transmitter gradients by symporting it with three sodium ions and a proton, and countertransporting a potassium ion via an elevator mechanism. Despite the availability of structures, the symport and antiport mechanisms still need to be clarified. We report high-resolution cryo-EM structures of human EAAT3 bound to the neurotransmitter glutamate with symported ions, potassium ions, sodium ions alone, or without ligands. We show that an evolutionarily conserved occluded translocation intermediate has a dramatically higher affinity for the neurotransmitter and the countertransported potassium ion than outward- or inward-facing transporters and plays a crucial role in ion coupling. We propose a comprehensive ion coupling mechanism involving a choreographed interplay between bound solutes, conformations of conserved amino acid motifs, and movements of the gating hairpin and the substrate-binding domain.
Topics: Humans; Amino Acid Transport System X-AG; Ion Transport; Ions; Glutamic Acid; Sodium; Potassium
PubMed: 37142617
DOI: 10.1038/s41467-023-38120-5 -
Journal of the American Society of... Apr 2016Hyperkalemia is common in patients with impaired kidney function or who take drugs that inhibit the renin-angiotensin-aldosterone axis. During the past decade,... (Review)
Review
Hyperkalemia is common in patients with impaired kidney function or who take drugs that inhibit the renin-angiotensin-aldosterone axis. During the past decade, substantial advances in understanding how the body controls potassium excretion have been made, which may lead to improved standard of care for these patients. Renal potassium disposition is primarily handled by a short segment of the nephron, comprising part of the distal convoluted tubule and the connecting tubule, and regulation results from the interplay between aldosterone and plasma potassium. When dietary potassium intake and plasma potassium are low, the electroneutral sodium chloride cotransporter is activated, leading to salt retention. This effect limits sodium delivery to potassium secretory segments, limiting potassium losses. In contrast, when dietary potassium intake is high, aldosterone is stimulated. Simultaneously, potassium inhibits the sodium chloride cotransporter. Because more sodium is then delivered to potassium secretory segments, primed by aldosterone, kaliuresis results. When these processes are disrupted, hyperkalemia results. Recently, new agents capable of removing potassium from the body and treating hyperkalemia have been tested in clinical trials. This development suggests that more effective and safer approaches to the prevention and treatment of hyperkalemia may be on the horizon.
Topics: Humans; Hyperkalemia; Kidney; Potassium
PubMed: 26510885
DOI: 10.1681/ASN.2015070751 -
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 -
Infection and Immunity Mar 2021Host colonization by a pathogen requires proper sensing and response to local environmental cues, to ensure adaptation and continued survival within the host. The ionic... (Review)
Review
Host colonization by a pathogen requires proper sensing and response to local environmental cues, to ensure adaptation and continued survival within the host. The ionic milieu represents a critical potential source of environmental cues, and indeed, there has been extensive study of the interplay between host and pathogen in the context of metals such as iron, zinc, and manganese, vital ions that are actively sequestered by the host. The inherent non-uniformity of the ionic milieu also extends, however, to "abundant" ions such as chloride and potassium, whose concentrations vary greatly between tissue and cellular locations, and with the immune response. Despite this, the concept of abundant ions as environmental cues and key players in host-pathogen interactions is only just emerging. Focusing on chloride and potassium, this review brings together studies across multiple bacterial and parasitic species that have begun to define both how these abundant ions are exploited as cues during host infection, and how they can be actively manipulated by pathogens during host colonization. The close links between ion homeostasis and sensing/response to different ionic signals, and the importance of studying pathogen response to cues in combination, are also discussed, while considering the fundamental insight still to be uncovered from further studies in this nascent area of inquiry.
Topics: Animals; Anions; Bacteria; Chlorides; Disease Susceptibility; Homeostasis; Host-Parasite Interactions; Host-Pathogen Interactions; Humans; Ions; Potassium
PubMed: 33526568
DOI: 10.1128/IAI.00641-20 -
Current Opinion in Nephrology and... Sep 2017The current review combines past findings with recent advances in our understanding of the homeostatic response to potassium imbalance. (Review)
Review
PURPOSE OF REVIEW
The current review combines past findings with recent advances in our understanding of the homeostatic response to potassium imbalance.
RECENT FINDINGS
Following the ingestion of a dietary potassium load, a combination of extrarenal and renal mechanisms act to maintain extracellular K+ within a tight window. Through hormonal regulation and direct K+ sensing, the nephron is ideally suited to respond to wide shifts in external K+ balance. Current evidence indicates that dietary K+ loading triggers a coordinated kaliuretic response that appears to involve voltage-dependent changes in sodium transport across multiple nephron segments, including the proximal tubule, medullary loop of Henle, and distal tubule. Inhibition of sodium transport in these segments would accomplish the final goal of enhancing distal NaCl delivery, luminal flow, and K+ secretion in the aldosterone sensitive distal nephron (ASDN).
SUMMARY
Ongoing research seeks to define the relationship between potassium and volume homeostasis by elucidating pathways that couple renal K+ sensing and tubular function during the potassium stress response.
Topics: Animals; Homeostasis; Humans; Ion Transport; Nephrons; Potassium; Potassium, Dietary; Sodium; Stress, Physiological
PubMed: 28614118
DOI: 10.1097/MNH.0000000000000352 -
PloS One 2024The selective separation of ions from aqueous systems, and even in the human body, is a crucial to overall environmental management and health. Nanoporous materials are...
The selective separation of ions from aqueous systems, and even in the human body, is a crucial to overall environmental management and health. Nanoporous materials are widely known for their selective removal of cations from aqueous media, and therefore have been targeted for use as a pharmaceutical to treat hyperkalemia. This study investigated the detailed crystallographic molecular mechanisms that control the potassium ion selectivity in the nanoporous cubic zirconium silicate (CZS) related materials. Using time-resolved in situ Raman spectroscopy and time-resolved in situ X-ray diffraction, the selectivity mechanisms were determined to involve a synchronous cation-cation repulsion process that serves to open a favorable coordination bonding environment for potassium, not unlike the ion selectivity filter process found in potassium ion channels in proteins. Enhancement of ion exchange was observed when the CZS material was in a partial protonated state (≈3:1 Na:H), causing an expansion of the unit-cell volume, enlargement of the 7 member-ring window, and distortion of framework polyhedra, which allowed increased accessibility to the cage structures and resulted in rapid irreversible potassium ion exchange.
Topics: Humans; Potassium; Protons; Hydrogen; Ion Exchange; Cations; Zirconium; Pharmaceutical Preparations; Silicates
PubMed: 38512829
DOI: 10.1371/journal.pone.0298661 -
Molecules (Basel, Switzerland) Sep 2022The adeninate anion (Ade) is a useful nucleophile used in the synthesis of many prodrugs (including those for HIV AIDS treatment). It exists as a contact ion-pair (CIP)...
The adeninate anion (Ade) is a useful nucleophile used in the synthesis of many prodrugs (including those for HIV AIDS treatment). It exists as a contact ion-pair (CIP) with Na and K (M) but the site of coordination is not obvious from spectroscopic data. Herein, a molecular-wide and electron density-based (MOWED) computational approach implemented in the implicit solvation model showed a strong preference for bidentate ion coordination at the N3 and N9 atoms. The N3N9-CIP has (i) the strongest inter-ionic interaction, by -30 kcal mol, with a significant (10-15%) covalent contribution, (ii) the most stabilized bonding framework for Ade, and (iii) displays the largest ion-induced polarization of Ade, rendering the N3 and N9 the most negative and, hence, most nucleophilic atoms. Alkylation of the adeninate anion at these two positions can therefore be readily explained when the metal coordinated complex is considered as the nucleophile. The addition of explicit DMSO solvent molecules did not change the trend in most nucleophilic N-atoms of Ade for the in-plane M-Ade complexes in M-Ade-(DMSO) molecular systems. MOWED-based studies of the strength and nature of interactions between DMSO solvent molecules and counter ions and Ade revealed an interesting and unexpected chemistry of intermolecular chemical bonding.
Topics: Anions; Dimethyl Sulfoxide; Electrons; Ions; Models, Molecular; Potassium; Prodrugs; Sodium; Solvents
PubMed: 36144844
DOI: 10.3390/molecules27186111