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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 -
Journal of the American Chemical Society Aug 2021K-channels are membrane proteins that regulate the selective conduction of potassium ions across cell membranes. Although the atomic mechanisms of K permeation have been...
K-channels are membrane proteins that regulate the selective conduction of potassium ions across cell membranes. Although the atomic mechanisms of K permeation have been extensively investigated, previous work focused on characterizing the selectivity and occupancy of the binding sites, the role of water molecules in the conduction process, or the identification of the minimum energy pathways enabling permeation. Here, we exploit molecular dynamics simulations and the analytical power of Markov state models to perform a comparative study of ion conduction in three distinct channel models. Significant differences emerged in terms of permeation mechanisms and binding site occupancy by potassium ions and/or water molecules from 100 μs cumulative trajectories. We found that, at odds with the current paradigm, each system displays a characteristic permeation mechanism, and thus, there is not a unique way by which potassium ions move through K-channels. The high functional diversity of K-channels can be attributed in part to the differences in conduction features that have emerged from this work. This study provides crucial information and further inspiration for wet-lab chemists designing new synthetic strategies to produce versatile artificial ion channels that emulate membrane transport for their applications in diagnosis, sensors, the next generation of water treatment technologies, etc., as the ability of synthetic channels to transport molecular ions across a bilayer in a controlled way is usually governed through the choice of metal ions, their oxidation states, or their coordination geometries.
Topics: Electric Conductivity; Ions; Molecular Dynamics Simulation; Potassium; Potassium Channels
PubMed: 34323472
DOI: 10.1021/jacs.1c04802 -
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 -
PloS One 2013Voltage-sensitive potassium ion channels are essential for life, but the molecular basis of their ion conduction is not well understood. In particular, the impact of ion...
Voltage-sensitive potassium ion channels are essential for life, but the molecular basis of their ion conduction is not well understood. In particular, the impact of ion concentration on ion conduction has not been fully studied. We performed several micro-second molecular dynamics simulations of the pore domain of the Kv1.2 potassium channel in KCl solution at four different ion concentrations, and scrutinized each of the conduction events, based on graphical representations of the simulation trajectories. As a result, we observed that the conduction mechanism switched with different ion concentrations: at high ion concentrations, potassium conduction occurred by Hodgkin and Keynes' knock-on mechanism, where the association of an incoming ion with the channel is tightly coupled with the dissociation of an outgoing ion, in a one-step manner. On the other hand, at low ion concentrations, ions mainly permeated by a two-step association/dissociation mechanism, in which the association and dissociation of ions were not coupled, and occurred in two distinct steps. We also found that this switch was triggered by the facilitated association of an ion from the intracellular side within the channel pore and by the delayed dissociation of the outermost ion, as the ion concentration increased.
Topics: Ion Transport; Ions; Kv1.2 Potassium Channel; Models, Biological; Models, Chemical; Models, Molecular; Molecular Dynamics Simulation; Potassium; Potassium Channels; Protein Conformation
PubMed: 23418558
DOI: 10.1371/journal.pone.0056342 -
Postgraduate Medicine Jun 2015Hypokalemia is a common electrolyte disturbance, observed in > 20% of hospitalized patients. Hypokalemia, although not formally defined, is generally considered to be... (Review)
Review
Hypokalemia is a common electrolyte disturbance, observed in > 20% of hospitalized patients. Hypokalemia, although not formally defined, is generally considered to be when serum potassium levels fall below the normal value of 3.6 mmol/L. In contrast to other electrolytes, potassium is primarily an intracellular ion: only 2% of all potassium in the body is present in the extracellular fluid, so a small decrease in serum potassium may represent a significant decrease in intracellular potassium. Individuals with mildly decreased potassium levels (3.0-3.5 mmol/L) may be asymptomatic, but patients with more pronounced decreases may report symptoms including muscle weakness, fatigue, and constipation. Very low serum potassium levels (≤ 2.5 mmol/L) can lead to muscle necrosis, paralysis, cardiac arrhythmias, and impaired respiration, which can be life-threatening. Absent comprehensive and robust treatment guidelines, strategies for the prevention or treatment of hypokalemia, such as how to diagnose hypokalemia, when to treat patients, what dosage regimen of potassium supplementation to use and for how long, are often based on the experience of the physician and empirical evidence. However, proper evaluation and treatment of hypokalemia in patients is essential because of associated morbidities. Because small potassium deficits in serum represent large body losses, potassium repletion requires substantial and prolonged supplementation. For patients with known risk factors for hypokalemia (e.g. hypertension, heart failure, or diabetes), careful monitoring is crucial to avoid the adverse sequelae associated with potassium deficits and to ensure that adequate and timely preventive measures can be taken. In this review, we provide practical insights into the etiology, differential diagnosis, and treatment of hypokalemia, including treatment strategies for patients with known risk factors.
Topics: Dietary Supplements; Humans; Hypokalemia; Potassium, Dietary
PubMed: 25960118
DOI: 10.1080/00325481.2015.1045814 -
Analytica Chimica Acta Nov 2018A conductometric sensor for potassium ions in solution is presented. Interdigitated, planar gold electrodes were coated with a potassium-selective polymer membrane...
A conductometric sensor for potassium ions in solution is presented. Interdigitated, planar gold electrodes were coated with a potassium-selective polymer membrane composed of a poly(vinyl chloride) matrix with about 65 wt% of plasticiser and 2-5 wt% of a potassium-selective ionophore. The impedance of the membrane was measured, using the electrodes as a transducer, and related to the concentration of potassium in a sample solution in contact with the membrane. Sensitivity was optimised by varying the sensor components, and selectivity for potassium over sodium was also shown. The resulting devices are compact, miniature, robust sensors which, by means of impedance measurements, eliminate the need for a reference electrode. The sensor was tested for potassium concentration changes of 2 mM across the clinically relevant range of 2.7-18.7 mM.
Topics: Electric Impedance; Electrochemical Techniques; Ions; Potassium
PubMed: 30193638
DOI: 10.1016/j.aca.2018.06.044 -
Journal of the American Society of... Jun 2023Rapid renal responses to ingested potassium are essential to prevent hyperkalemia and also play a central role in blood pressure regulation. Although local extracellular...
SIGNIFICANCE STATEMENT
Rapid renal responses to ingested potassium are essential to prevent hyperkalemia and also play a central role in blood pressure regulation. Although local extracellular K + concentration in kidney tissue is increasingly recognized as an important regulator of K + secretion, the underlying mechanisms that are relevant in vivo remain controversial. To assess the role of the signaling kinase mTOR complex-2 (mTORC2), the authors compared the effects of K + administered by gavage in wild-type mice and knockout mice with kidney tubule-specific inactivation of mTORC2. They found that mTORC2 is rapidly activated to trigger K + secretion and maintain electrolyte homeostasis. Downstream targets of mTORC2 implicated in epithelial sodium channel regulation (SGK1 and Nedd4-2) were concomitantly phosphorylated in wild-type, but not knockout, mice. These findings offer insight into electrolyte physiologic and regulatory mechanisms.
BACKGROUND
Increasing evidence implicates the signaling kinase mTOR complex-2 (mTORC2) in rapid renal responses to changes in plasma potassium concentration [K + ]. However, the underlying cellular and molecular mechanisms that are relevant in vivo for these responses remain controversial.
METHODS
We used Cre-Lox-mediated knockout of rapamycin-insensitive companion of TOR (Rictor) to inactivate mTORC2 in kidney tubule cells of mice. In a series of time-course experiments in wild-type and knockout mice, we assessed urinary and blood parameters and renal expression and activity of signaling molecules and transport proteins after a K + load by gavage.
RESULTS
A K + load rapidly stimulated epithelial sodium channel (ENaC) processing, plasma membrane localization, and activity in wild-type, but not in knockout, mice. Downstream targets of mTORC2 implicated in ENaC regulation (SGK1 and Nedd4-2) were concomitantly phosphorylated in wild-type, but not knockout, mice. We observed differences in urine electrolytes within 60 minutes, and plasma [K + ] was greater in knockout mice within 3 hours of gavage. Renal outer medullary potassium (ROMK) channels were not acutely stimulated in wild-type or knockout mice, nor were phosphorylation of other mTORC2 substrates (PKC and Akt).
CONCLUSIONS
The mTORC2-SGK1-Nedd4-2-ENaC signaling axis is a key mediator of rapid tubule cell responses to increased plasma [K + ] in vivo . The effects of K + on this signaling module are specific, in that other downstream mTORC2 targets, such as PKC and Akt, are not acutely affected, and ROMK and Large-conductance K + (BK) channels are not activated. These findings provide new insight into the signaling network and ion transport systems that underlie renal responses to K +in vivo .
Topics: Mice; Animals; Phosphorylation; Potassium; Epithelial Sodium Channels; Protein Serine-Threonine Kinases; Potassium, Dietary; TOR Serine-Threonine Kinases; Proto-Oncogene Proteins c-akt; Immediate-Early Proteins; Mechanistic Target of Rapamycin Complex 2; Kidney; Carrier Proteins; Mice, Knockout; Ion Transport
PubMed: 36890646
DOI: 10.1681/ASN.0000000000000109 -
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 -
American Journal of Physiology.... Mar 2006Unlike sodium, potassium is vasoactive; for example, when infused into the arterial supply of a vascular bed, blood flow increases. The vasodilation results from... (Review)
Review
Unlike sodium, potassium is vasoactive; for example, when infused into the arterial supply of a vascular bed, blood flow increases. The vasodilation results from hyperpolarization of the vascular smooth muscle cell subsequent to potassium stimulation by the ion of the electrogenic Na+-K+ pump and/or activating the inwardly rectifying Kir channels. In the case of skeletal muscle and brain, the increased flow sustains the augmented metabolic needs of the tissues. Potassium ions are also released by the endothelial cells in response to neurohumoral mediators and physical forces (such as shear stress) and contribute to the endothelium-dependent relaxations, being a component of endothelium-derived hyperpolarization factor-mediated responses. Dietary supplementation of potassium can lower blood pressure in normal and some hypertensive patients. Again, in contrast to NaCl restriction, the response to potassium supplementation is slow to appear, taking approximately 4 wk. Such supplementation reduces the need for antihypertensive medication. "Salt-sensitive" hypertension responds particularly well, perhaps, in part, because supplementation with potassium increases the urinary excretion of sodium chloride. Potassium supplementation may even reduce organ system complications (e.g., stroke).
Topics: Animals; Blood Flow Velocity; Blood Pressure; Feedback; Hemostasis; Humans; Hypertension; Potassium; Potassium Channels; Potassium, Dietary; Sodium Chloride, Dietary; Sodium-Potassium-Exchanging ATPase
PubMed: 16467502
DOI: 10.1152/ajpregu.00491.2005 -
Advanced Materials (Deerfield Beach,... Jul 2014Ion-selective organic electrochemical transistors with sensitivity to potassium approaching 50 μA dec(-1) are demonstrated. The remarkable sensitivity arises from the...
Ion-selective organic electrochemical transistors with sensitivity to potassium approaching 50 μA dec(-1) are demonstrated. The remarkable sensitivity arises from the use of high transconductance devices, where the conducting polymer is in direct contact with a reference gel electrolyte and integrated with an ion-selective membrane.
Topics: Biosensing Techniques; Conductometry; Equipment Design; Equipment Failure Analysis; Ions; Membranes, Artificial; Organic Chemicals; Polyvinyl Chloride; Potassium; Transistors, Electronic
PubMed: 24862110
DOI: 10.1002/adma.201400731