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Science Advances Feb 2019Reproducing the exquisite ion selectivity displayed by biological ion channels in artificial nanopore systems has proven to be one of the most challenging tasks...
Reproducing the exquisite ion selectivity displayed by biological ion channels in artificial nanopore systems has proven to be one of the most challenging tasks undertaken by the nanopore community, yet a successful achievement of this goal offers immense technological potential. Here, we show a strategy to design solid-state nanopores that selectively transport potassium ions and show negligible conductance for sodium ions. The nanopores contain walls decorated with 4'-aminobenzo-18-crown-6 ether and single-stranded DNA (ssDNA) molecules located at one pore entrance. The ionic selectivity stems from facilitated transport of potassium ions in the pore region containing crown ether, while the highly charged ssDNA plays the role of a cation filter. Achieving potassium selectivity in solid-state nanopores opens new avenues toward advanced separation processes, more efficient biosensing technologies, and novel biomimetic nanopore systems.
Topics: Biomimetics; Models, Theoretical; Nanopores; Nanotechnology; Phase Transition; Potassium
PubMed: 30783627
DOI: 10.1126/sciadv.aav2568 -
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 -
Seminars in Nephrology Nov 2018In the United States, end-stage renal disease patients receiving hemodialysis have an exceedingly high risk of sudden cardiac death (SCD), accounting for 29% of death... (Review)
Review
In the United States, end-stage renal disease patients receiving hemodialysis have an exceedingly high risk of sudden cardiac death (SCD), accounting for 29% of death events, likely relating to their uremic milieu, recurring exposure to fluid and electrolyte fluxes, and underlying cardiovascular pathology. Furthermore, epidemiologic studies have shown that SCD events, as well as mortality and hospitalizations, occur most frequently on the first dialysis day after the long interdialytic gap, suggesting that abrupt fluctuations in the accumulation and removal of electrolytes, fluid, and uremic toxins over the dialysis cycle may be contributory. Some population-based observational studies have suggested that lower dialysate potassium concentrations appear to be associated with a heightened risk of postdialysis cardiac arrest in hemodialysis patients, although the optimal serum-to-dialysate potassium gradient remains unclear. Some observational studies have suggested that low dialysate calcium concentrations and high serum-to-dialysate calcium gradients may predispose patients to SCD. There is ongoing controversy about an association between higher dialysate bicarbonate concentrations and higher risk of cardiac arrest, likely owing to confounding by indication. Some observational studies also have shown that large interdialytic weight gains, fluid retention, and high ultrafiltration rates are linked with higher risk of SCD and mortality. However, there remains considerable controversy regarding the pros and cons of designating a specific upper ultrafiltration limit with extended treatment times as a clinical practice measure, and further studies are needed to define the optimal tools, metrics, targets, and implementation measures for volume control in the hemodialysis population. In this review, we highlight the epidemiology and pathophysiology of how specific aspects of the hemodialysis procedure may relate to the risk of SCD, as well as preventative strategies and future research directions that can address this risk.
Topics: Acid-Base Imbalance; Bicarbonates; Calcium; Death, Sudden, Cardiac; Hemodialysis Solutions; Humans; Kidney Failure, Chronic; Magnesium; Potassium; Renal Dialysis; Time Factors; Water-Electrolyte Balance
PubMed: 30413252
DOI: 10.1016/j.semnephrol.2018.08.003 -
Neurochemistry International Jun 2020Glia use multiple mechanisms to mediate potassium fluxes that support neuronal function. In addition to changes in potassium levels within synapses, these ions are... (Review)
Review
Glia use multiple mechanisms to mediate potassium fluxes that support neuronal function. In addition to changes in potassium levels within synapses, these ions are dynamically dispersed through the interstitial parenchyma, perivascular spaces, leptomeninges, cerebrospinal fluid, choroid plexus, blood, vitreous, and endolymph. Neural circuits drive diversity in the glia that buffer potassium and this is reciprocal. Glia mediate buffering of potassium locally at glial-neuronal interfaces and via widespread networked connections. Control of potassium levels in the central nervous system is mediated by mechanisms operating at various loci with complexity that is difficult to model. However, major components of networked glial buffering are known. The role that potassium buffering plays in homeostasis of the CNS underlies some pathologic phenomena. An overview of potassium fluxes in the CNS is relevant for understanding consequences of pathogenic sequence variants in genes that encode potassium buffering proteins. Potassium flows in the CNS are described as follows: K1, the coordinated potassium fluxes within the astrocytic cradle around the synapse; K2, temporary storage of potassium within astrocytic processes in proposed microdomains; K3, potassium fluxes between oligodendrocytes and astrocytes; K4, potassium fluxes between astrocytes; K5, astrocytic potassium flux mediation of neurovasular coupling; K6, CSF delivery of potassium to perivascular spaces with dispersion to interstitial fluid between astrocytic endfeet; K7, astrocytic delivery of potassium to CSF and K8, choroid plexus (modified glia) regulation of potassium at the blood-CSF barrier. Components, mainly potassium channels, transporters, connexins and modulators, and the pathogenic sequence variants of their genes with the associated diseases are described.
Topics: Animals; Astrocytes; Central Nervous System; Homeostasis; Humans; Neuroglia; Oligodendroglia; Potassium
PubMed: 32194142
DOI: 10.1016/j.neuint.2020.104727 -
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 -
International Journal of Molecular... Nov 2023Potassium is essential for plant growth and development and stress adaptation. The maintenance of potassium homeostasis involves a series of potassium channels and... (Review)
Review
Potassium is essential for plant growth and development and stress adaptation. The maintenance of potassium homeostasis involves a series of potassium channels and transporters, which promote the movement of potassium ions (K) across cell membranes and exhibit complex expression patterns and regulatory mechanisms. Rice is a major food crop in China. The low utilization rate of potassium fertilizer limits the yield and quality of rice. Elucidating the molecular mechanisms of potassium absorption, transport, and utilization is critical in improving potassium utilization efficiency in rice. Although some K transporter genes have been identified from rice, research on the regulatory network is still in its infancy. Therefore, this review summarizes the relevant information on K channels and transporters in rice, covering the absorption of K in the roots, transport to the shoots, the regulation pathways, the relationship between K and the salt tolerance of rice, and the synergistic regulation of potassium, nitrogen, and phosphorus signals. The related research on rice potassium nutrition has been comprehensively reviewed, the existing research foundation and the bottleneck problems to be solved in this field have been clarified, and the follow-up key research directions have been pointed out to provide a theoretical framework for the cultivation of potassium-efficient rice.
Topics: Potassium; Oryza; Cation Transport Proteins; Salt Tolerance; Ions; Plant Roots; Gene Expression Regulation, Plant; Plant Proteins
PubMed: 38069005
DOI: 10.3390/ijms242316682 -
Annual Review of Biophysics May 2017In addition to continuous rapid progress in RNA structure determination, probing, and biophysical studies, the past decade has seen remarkable advances in the... (Review)
Review
In addition to continuous rapid progress in RNA structure determination, probing, and biophysical studies, the past decade has seen remarkable advances in the development of a new generation of RNA folding theories and models. In this article, we review RNA structure prediction models and models for ion-RNA and ligand-RNA interactions. These new models are becoming increasingly important for a mechanistic understanding of RNA function and quantitative design of RNA nanotechnology. We focus on new methods for physics-based, knowledge-based, and experimental data-directed modeling for RNA structures and explore the new theories for the predictions of metal ion and ligand binding sites and metal ion-dependent RNA stabilities. The integration of these new methods with theories about the cellular environment effects in RNA folding, such as molecular crowding and cotranscriptional kinetic effects, may ultimately lead to an all-encompassing RNA folding model.
Topics: Cations; Databases, Nucleic Acid; Kinetics; Ligands; Magnesium; Metals; Models, Molecular; Nucleic Acid Conformation; Potassium; RNA; Sodium; Thermodynamics
PubMed: 28301768
DOI: 10.1146/annurev-biophys-070816-033920 -
Nephrology, Dialysis, Transplantation :... May 2023Renin-angiotensin-aldosterone system inhibitors (RAASi) and mineralocorticoid receptor antagonists (MRAs) are important interventions to improve outcomes in patients...
Renin-angiotensin-aldosterone system inhibitors (RAASi) and mineralocorticoid receptor antagonists (MRAs) are important interventions to improve outcomes in patients with chronic kidney disease and heart failure, but their use is limited in some patients by the development of hyperkalemia. The risk of hyperkalemia may differ between agents, with one trial showing lower risk of hyperkalemia with the novel non-steroidal MRA finerenone compared with steroidal MRA spironolactone. Novel potassium binders, including patiromer and sodium zirconium cyclosilicate, are available interventions to manage hyperkalemia and enable continuation of RAASi and MRAs in patients who could benefit from these treatments. These agents bind free potassium ions in the lumen of the gastrointestinal tract to prevent the absorption of dietary potassium and increase potassium secretion. Several studies showed that potassium binders are effective compared with placebo for preventing hyperkalemia or steroidal MRA discontinuation, but none has evaluated whether this strategy impacts clinically important endpoints such as cardiovascular events. Due to this and other limitations related to cost, clinical availability, pill burden and patient selection, alternative potential strategies to mitigate hyperkalemia may be more practical. Conservative strategies include increased monitoring and use of loop or thiazide diuretics to increase urinary potassium excretion. Non-steroidal MRAs may have a lower risk of hyperkalemia than steroidal MRAs and have stronger anti-inflammatory and anti-fibrotic effects with resultant reduced risk of kidney disease progression. Sodium-glucose cotransporter-2 inhibitors also decrease hyperkalemia risk in patients on MRAs and decrease cardiovascular events and kidney disease progression. These may be better first-line interventions to obviate the need for potassium binders and offer additional benefits.
Topics: Humans; Disease Progression; Heart Failure; Hyperkalemia; Mineralocorticoid Receptor Antagonists; Potassium; Renal Insufficiency, Chronic; Renin-Angiotensin System; Sodium-Glucose Transporter 2 Inhibitors; Steroids
PubMed: 36264349
DOI: 10.1093/ndt/gfac284 -
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