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The Journal of General Physiology Feb 2023Inward-rectifier potassium channels (Kirs) are lipid-gated ion channels that differ from other K+ channels in that they allow K+ ions to flow more easily into, rather...
Inward-rectifier potassium channels (Kirs) are lipid-gated ion channels that differ from other K+ channels in that they allow K+ ions to flow more easily into, rather than out of, the cell. Inward rectification is known to result from endogenous magnesium ions or polyamines (e.g., spermine) binding to Kirs, resulting in a block of outward potassium currents, but questions remain regarding the structural and dynamic basis of the rectification process and lipid-dependent channel activation. Here, we present the results of long-timescale molecular dynamics simulations starting from a crystal structure of phosphatidylinositol 4,5-bisphosphate (PIP2)-bound chicken Kir2.2 with a non-conducting pore. After introducing a mutation (G178R) that is known to increase the open probability of a homologous channel, we were able to observe transitions to a stably open, ion-conducting pore, during which key conformational changes occurred in the main activation gate and the cytoplasmic domain. PIP2 binding appeared to increase stability of the pore in its open and conducting state, as PIP2 removal resulted in pore closure, with a median closure time about half of that with PIP2 present. To investigate structural details of inward rectification, we simulated spermine binding to and unbinding from the open pore conformation at positive and negative voltages, respectively, and identified a spermine-binding site located near a previously hypothesized site between the pore cavity and the selectivity filter. We also studied the effects of long-range electrostatics on conduction and spermine binding by mutating charged residues in the cytoplasmic domain and found that a finely tuned charge density, arising from basic and acidic residues within the cytoplasmic domain, modulated conduction and rectification.
Topics: Potassium Channels, Inwardly Rectifying; Spermine; Polyamines; Potassium; Lipids; Oocytes
PubMed: 36524993
DOI: 10.1085/jgp.202213085 -
Physiological Reports Mar 2022Cations such as Cs and Ba are known to block K currents by entering an open channel and binding to the selectivity filter, where they obstruct the pore and block...
Cations such as Cs and Ba are known to block K currents by entering an open channel and binding to the selectivity filter, where they obstruct the pore and block diffusion of the permeant ion. This obstruction is voltage- and K -dependent and is relieved by the trans permeant ion flux. The present patch-clamp study on Xenopus muscle cells shows that, unlike the voltage-activated K (Kv) channels, blockade of the inward rectifier K (Kir) channels by external foreign cations results from the combination of pore obstruction with a new and independent mechanism. This new blockade is independent of the K concentrations and flux and acts indiscriminately on both the outward and the inward Kir components. External Cs and Ba compete for this blockade with free access to common channel sites. These features suggest that the blocking cations do not need to enter the channel for this new mechanism, and should bind to the extracellular side of the channel. When K fluxes are flowing outward, the pore obstruction is relieved for both Kir and Kv currents, and the K -independent blockade here described is responsible for a selective Kir inhibition, justifying the use of these external cations as tools in cell physiology studies.
Topics: Animals; Cations; Potassium; Xenopus laevis
PubMed: 35274814
DOI: 10.14814/phy2.15200 -
Nature Communications Jan 2022Ion currents through potassium channels are gated. Constriction of the ion conduction pathway at the inner helix bundle, the textbook gate of Kir potassium channels, has...
Ion currents through potassium channels are gated. Constriction of the ion conduction pathway at the inner helix bundle, the textbook gate of Kir potassium channels, has been shown to be an ineffective permeation control, creating a rift in our understanding of how these channels are gated. Here we present evidence that anionic lipids act as interactive response elements sufficient to gate potassium conduction. We demonstrate the limiting barrier to K permeation lies within the ion conduction pathway and show that this gate is operated by the fatty acyl tails of lipids that infiltrate the conduction pathway via fenestrations in the walls of the pore. Acyl tails occupying a surface groove extending from the cytosolic interface to the conduction pathway provide a potential means of relaying cellular signals, mediated by anionic lipid head groups bound at the canonical lipid binding site, to the internal gate.
Topics: Anions; Binding Sites; Crystallography, X-Ray; Humans; Ion Channel Gating; Ion Transport; Liposomes; Membrane Lipids; Molecular Dynamics Simulation; Mutation; Phosphatidylcholines; Phosphatidylserines; Potassium; Potassium Channels, Inwardly Rectifying
PubMed: 35079013
DOI: 10.1038/s41467-022-28148-4 -
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 -
Ugeskrift For Laeger Sep 2014The hospitalized patient is at risk of hyponatraemia caused by reduced electrolyte free water clearance and prescription of hypotonic fluids. Hospital-acquired... (Review)
Review
The hospitalized patient is at risk of hyponatraemia caused by reduced electrolyte free water clearance and prescription of hypotonic fluids. Hospital-acquired hyponatraemia is common and associated with increased mortality/morbidity. Hyponatraemia in itself can cause severe cerebral symptoms. Small decreases in P-[Na⁺] in patients with reduced intracranial compliance (e.g. meningitis) can be dangerous. To reduce iatrogenic hyponatraemia the understanding of P-[Na+] is fundamental. Next, meticulously prescription of fluid amount/quality and reevaluation as with any other drug is of paramount importance.
Topics: Cations; Fluid Therapy; Humans; Hyponatremia; Iatrogenic Disease; Potassium; Sodium; Water-Electrolyte Balance
PubMed: 25293861
DOI: No ID Found -
International Journal of Molecular... Sep 2021Bone-forming cells or osteoblasts play an important role in bone modeling and remodeling processes. Osteoblast differentiation or osteoblastogenesis is orchestrated by... (Review)
Review
Bone-forming cells or osteoblasts play an important role in bone modeling and remodeling processes. Osteoblast differentiation or osteoblastogenesis is orchestrated by multiple intracellular signaling pathways (e.g., bone morphogenetic proteins (BMP) and Wnt signaling pathways) and is modulated by the extracellular environment (e.g., parathyroid hormone (PTH), vitamin D, transforming growth factor β (TGF-β), and integrins). The regulation of bone homeostasis depends on the proper differentiation and function of osteoblast lineage cells from osteogenic precursors to osteocytes. Intracellular Ca signaling relies on the control of numerous processes in osteoblast lineage cells, including cell growth, differentiation, migration, and gene expression. In addition, hyperpolarization via the activation of K channels indirectly promotes Ca signaling in osteoblast lineage cells. An improved understanding of the fundamental physiological and pathophysiological processes in bone homeostasis requires detailed investigations of osteoblast lineage cells. This review summarizes the current knowledge on the functional impacts of K channels and Ca-permeable channels, which critically regulate Ca signaling in osteoblast lineage cells to maintain bone homeostasis.
Topics: Animals; Calcium; Calcium Channels; Cations; Humans; Osteoblasts; Osteogenesis; Potassium; Potassium Channels; Signal Transduction
PubMed: 34638799
DOI: 10.3390/ijms221910459 -
International Journal of Nanomedicine 2022Plasma albumins as protein nanoparticles (PNs) exert essential functions in the control of biological osmotic pressure (OP), being involved in regulating water...
INTRODUCTION
Plasma albumins as protein nanoparticles (PNs) exert essential functions in the control of biological osmotic pressure (OP), being involved in regulating water metabolism, cell morphology and cell tension. Understanding how plasma albumins and different electrolytes co-determine biological OP effects is crucial for correct interpretation of hemodynamic disorders, and practical treatment of hypo/hyper-proteinemia.
METHODS
Optical measurement based on intermediate filament (IF) tension probe was used for real-time evaluation of transmembrane osmotic effects in live cells. Ion fluorescent probes were employed to evaluate intracellular ion levels, and a current clamp was used to measure membrane potential, thus exploring association of electrochemical and osmotic effects.
RESULTS
Albumins are involved in regulation of intracellular osmolarity by a quantitative relationship. Extracellular PNs can alter membrane potentials by adsorbing counterions, induce production of intracellular PNs and further control the opening of ion channels and ion flow, contributing to electrochemical and osmotic re-equilibrium. Furthermore, various ions interplay with extracellular PNs, showing different osmotic effects: increased levels of calcium ions result in a hypotonic effect, whereas potassium ions induce hyper-osmolarity.
CONCLUSION
Extracellular PNs and Ca/K display antagonistic or synergetic effects in regulating biological OP. Live cells can spontaneously regulate osmotic effects through changing membrane potential and controlling intracellular ion content. Various plasma components need to be comprehensively analyzed, further developing a diagnostic index that considers the biological OP effects of various blood components and improves the evaluation of symptoms and diseases, such as calcium/potassium-hemodynamic disorders and edema.
Topics: Albumins; Body Water; Calcium; Fluorescent Dyes; Humans; Ion Channels; Ions; Nanoparticles; Osmotic Pressure; Potassium
PubMed: 36238535
DOI: 10.2147/IJN.S383530 -
Experimental Physiology Apr 2021What is the central question of this study? What are the mechanisms by which equine sweat glands transport sodium, potassium and water into sweat? What is the main...
NEW FINDINGS
What is the central question of this study? What are the mechanisms by which equine sweat glands transport sodium, potassium and water into sweat? What is the main finding and its importance? The flux of sodium into sweat does not have an active transport component, the flux of potassium into sweat is partially dependent on an active transport mechanism, and there is no evidence for paracellular transport.
ABSTRACT
In two series of experiments, this study used radioactive sodium (Na ) and potassium (K ) to trace the net flux, and calculate the unidirectional fluxes, of these ions from extracellular fluid into sweat of horses during exercise and recovery. The effect of an oral electrolyte supplement (PNW) on the sweating responses and ion fluxes was also examined. Compared to 8 litres of water (controls), provision of 8 litres of PNW resulted in significantly increased sweating duration (P < 0.001). Two hours before exercise, Tc-labelled diethylene-triamine-pentaacetate (DTPA) was administered i.v. to determine if there was paracellular flux of this molecule in sweat glands during the period of sweating. One hour before beginning moderate-intensity exercise, horses were nasogastrically administered either Na (1-3 litres) or K (8 litres) with water (control) or an electrolyte supplement. Both radiotracers appeared in sweat within 10 min of exercise onset, and the sweat specific activity of both ions increased during exercise (P < 0.001), approaching plasma specific activities. There was no appearance of Tc-DTPA in sweat. The activities of Na and K, together with the concentrations Na , K and Cl , argued against significant paracellular flux of these ions into the lumen of sweat glands. The flux analysis for Na indicated a small intracellular pool within sweat gland cells, and no evidence for an active transport component. The flux analysis for K indicated a relatively large intracellular equilibration pool within sweat gland cells, with evidence for an active transport component. The results are discussed with respect to the current understanding of sweat gland epithelial cell ion transport mechanisms at both the basal and the apical membranes. It appears likely that the majority of ions appearing in sweat pass through sweat gland epithelial cells by transcellular mechanisms that include ion transporting pathways as well as apical vesicular exocytosis.
Topics: Animals; Chlorides; Horses; Physical Conditioning, Animal; Potassium; Sodium; Sweat; Sweating; Water
PubMed: 33550621
DOI: 10.1113/EP089232 -
PloS One 2022Soil water soluble base ion salt-based ion concentrations are critical parameters for estimating soil buffer capacity and vegetation productivity. Ionic content clearly...
Soil water soluble base ion salt-based ion concentrations are critical parameters for estimating soil buffer capacity and vegetation productivity. Ionic content clearly covaries with the distribution of plant communities. Previous studies on salt-based ions in soils focused primarily on ion migration and its relationships with vegetation growth. Few studies have sought to characterize larger scale spatial distribution of salt-based ions or correlation with climatic and plant community characteristics. This study used ion chromatography to analyze the salt-based ion content (Ca2+, Mg2+, Na+ and K+) of surface soils from the Hunshandake sandy lands. Statistical methods were used interpret spatial variation. Results showed that the average content of salt-based ions in Hunshandake sandy land was 86.57 mg/kg. Average values ranked as Ca2+ > Na+ > K+ > Mg2+ but concentrations also exhibited uneven spatial distributions. Horizontal spatial variation in Ca2+, Mg2+ and Na+ ions showed these ions gradually decrease from northwest to southeast. Potassium ions (K+) showed no obvious spatial variation trends. Ions varied significantly across different soil layers but their average concentrations ranked as K+>Na+>Ca2+>Mg2+ (from shallow to deep). The 20-30 cm soil layer contained the highest salt ion concentrations. Of the four base ions, only K+ ions appeared in surface samples. In terms of water soluble base ion available salt-based ions, Ca2+ occurred in the highest concentrations along the north and west side of the study area. K+ ions occurred in the highest concentrations along the south and east sides of the study area. Na+ concentrations did not show a consistent spatial pattern. Statistical analysis detected significant correlations of normalized ion concentration parameters (Ca2+/CECT, K+/CEC, effective water soluble base ion salt-based ions) and the total species number, average species number and total biomass of the plant communities (P <0.05). This study can help inform understanding of soil water transport in sandy areas and provide a reference for interpreting ecosystems in arid regions.
Topics: Calcium; China; Ecosystem; Ions; Magnesium; Plants; Potassium; Sand; Sodium; Sodium Chloride; Sodium Chloride, Dietary; Soil; Water
PubMed: 35930614
DOI: 10.1371/journal.pone.0271562 -
Toxins Sep 2022Hyperkalemia is a major concern in chronic kidney disease and in end-stage renal disease, representing a predictor of hospitalization and mortality. To prevent and treat...
Hyperkalemia is a major concern in chronic kidney disease and in end-stage renal disease, representing a predictor of hospitalization and mortality. To prevent and treat hyperkalemia, dietary management is of great clinical interest. Currently, the growing use of plant-based diets causes an increasing concern about potassium load in renal patients. The aim of this study was to assess the bioaccessibility of potassium in vegetables, concerning all aspects of the plants (fruit, flower, root, tuber, leaf and seed) and to what extent different boiling techniques affect potassium content and bioaccessibility of plant-based foods. Bioaccessibility was evaluated by an in vitro digestion methodology, resembling human gastro-intestinal tract. Potassium content was higher in seeds and leaves, despite it not being possible to define a common "rule" according to the type of organ, namely seed, leaf or fruit. Boiling reduced potassium content in all vegetables excluding carrot, zucchini, and cauliflower; boiling starting from cold water contributed to a greater reduction of the potassium content in potato, peas, and beans. Bioaccessibility after in vitro digestion ranged from 12 (peas) to 93% (tomato) regardless of species and organs. Higher bioaccessibility was found in spinach, chicory, zucchini, tomato, kiwi, and cauliflower, and lower bioaccessibility in peas. Potassium from leaf resulted in the highest bioaccessibility after digestion; as a whole potassium bioaccessibility in the fruits and vegetables studied was 67% on average, with differences in relation to the different organs and species. Further, considering the method of boiling to reduce potassium content, these data indicate that the effective potassium load from plant-based foods may be lower than originally expected. This supports the clinical advices to maintain a wide use of plant-based food in the management of renal patients.
Topics: Humans; Potassium; Hyperkalemia; Digestion; Vegetables; Brassica; Solanum lycopersicum; Water; Biological Availability
PubMed: 36287937
DOI: 10.3390/toxins14100668