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Proceedings of the National Academy of... Jun 2023In bacterial voltage-gated sodium channels, the passage of ions through the pore is controlled by a selectivity filter (SF) composed of four glutamate residues. The...
In bacterial voltage-gated sodium channels, the passage of ions through the pore is controlled by a selectivity filter (SF) composed of four glutamate residues. The mechanism of selectivity has been the subject of intense research, with suggested mechanisms based on steric effects, and ion-triggered conformational change. Here, we propose an alternative mechanism based on ion-triggered shifts in p values of SF glutamates. We study the NaMs channel for which the open channel structure is available. Our free-energy calculations based on molecular dynamics simulations suggest that p values of the four glutamates are higher in solution of K ions than in solution of Na ions. Higher p in the presence of K stems primarily from the higher population of dunked conformations of the protonated Glu sidechain, which exhibit a higher p shift. Since p values are close to the physiological pH, this results in predominant population of the fully deprotonated state of glutamates in Na solution, while protonated states are predominantly populated in K solution. Through molecular dynamics simulations we calculate that the deprotonated state is the most conductive, the singly protonated state is less conductive, and the doubly protonated state has significantly reduced conductance. Thus, we propose that a significant component of selectivity is achieved through ion-triggered shifts in the protonation state, which favors more conductive states for Na ions and less conductive states for K ions. This mechanism also suggests a strong pH dependence of selectivity, which has been experimentally observed in structurally similar NaChBac channels.
Topics: Ions; Bacteria; Molecular Dynamics Simulation; Voltage-Gated Sodium Channels; Glutamates; Potassium
PubMed: 37339196
DOI: 10.1073/pnas.2220343120 -
International Journal of Molecular... Jun 2023In this paper, the influence of external terahertz electromagnetic fields with different frequencies of 4 THz, 10 THz, 15 THz, and 20 THz on the permeability of the...
In this paper, the influence of external terahertz electromagnetic fields with different frequencies of 4 THz, 10 THz, 15 THz, and 20 THz on the permeability of the Kv1.2 voltage-gated potassium ion channel on the nerve cell membrane was studied using the combined model of the "Constant Electric Field-Ion Imbalance" method by molecular dynamics. We found that although the applied terahertz electric field does not produce strong resonance with the -C=O groups of the conservative sequence T-V-G-Y-G amino acid residue of the selective filter (SF) of the channel, it would affect the stability of the electrostatic bond between potassium ions and the carbonyl group of T-V-G-Y-G of SF, and it would affect the stability of the hydrogen bond between water molecules and oxygen atoms of the hydroxyl group of the 374THR side chain at the SF entrance, changing the potential and occupied states of ions in the SF and the occurrence probability of the permeation mode of ions and resulting in the change in the permeability of the channel. Compared with no external electric field, when the external electric field with 15 THz frequency is applied, the lifetime of the hydrogen bond is reduced by 29%, the probability of the "soft knock on" mode is decreased by 46.9%, and the ion flux of the channel is activated by 67.7%. Our research results support the view that compared to "direct knock-on", "soft knock-on" is a slower permeation mode.
Topics: Electromagnetic Fields; Potassium Channels, Voltage-Gated; Molecular Dynamics Simulation; Ions; Permeability; Potassium; Kv1.2 Potassium Channel; Kv1.5 Potassium Channel
PubMed: 37373419
DOI: 10.3390/ijms241210271 -
The International Journal of... 2008Whole-cell voltage clamp of mammalian spermatozoa was first achieved in 2006. This technical advance, combined with genetic deletion strategies, makes unambiguous... (Review)
Review
Whole-cell voltage clamp of mammalian spermatozoa was first achieved in 2006. This technical advance, combined with genetic deletion strategies, makes unambiguous identification of sperm ion channel currents possible. This review summarizes the ion channel currents that have been directly measured in mammalian sperm, and their physiological roles in fertilization. The predominant currents are a Ca2+-selective current requiring expression of the 4 mCatSper genes, and a rectifying K+ current with properties most similar to mSlo3. Intracellular alkalinization activates both channels and induces hyperactivated motility.
Topics: Amino Acid Sequence; Animals; Calcium; Female; Fertility; Fertilization; Humans; Ion Channels; Ions; Male; Molecular Sequence Data; Potassium; Protein Conformation; Sperm Motility; Spermatozoa
PubMed: 18649274
DOI: 10.1387/ijdb.072554bn -
Function (Oxford, England) 2022Hyperpolarization-activated cyclic nucleotide-gated (HCN) channels generate the pacemaker current which plays an important role in the timing of various biological...
Hyperpolarization-activated cyclic nucleotide-gated (HCN) channels generate the pacemaker current which plays an important role in the timing of various biological processes like the heart beat. We used umbrella sampling to explore the potential of mean force for the conduction of potassium and sodium through the open HCN4 pore. Our data explain distinct functional features like low unitary conductance and weak selectivity as a result of high energetic barriers inside the selectivity filter of this channel. They exceed the 3-5 kJ/mol threshold which is presumed as maximal barrier for diffusion-limited conductance. Furthermore, simulations provide a thermodynamic explanation for the weak cation selectivity of HCN channels that contain only two ion binding sites in the selectivity filter (SF). We find that sodium ions bind more strongly to the SF than potassium and are easier released by binding of potassium than of another sodium. Hence ion transport and selectivity in HCN channels is not determined by the same mechanism as in potassium-selective channels; it rather relies on sodium as a weak blocker that can only be released by potassium.
Topics: Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels; Potassium Channels; Cations; Binding Sites; Sodium; Potassium
PubMed: 36156894
DOI: 10.1093/function/zqac019 -
Biophysical Journal May 1962Squid giant axons loaded with Na(24) were subjected to short duration (0.5 msec.) clamped depolarizations of about 100 mv at frequencies of 20/sec. and 60/sec. while in...
Squid giant axons loaded with Na(24) were subjected to short duration (0.5 msec.) clamped depolarizations of about 100 mv at frequencies of 20/sec. and 60/sec. while in choline sea water. Under such conditions the early outward current was just about maximal at the time of termination of the clamping pulse. An integration of the early current versus time record gave 1.2 mucoulomb/cm(2) pulse, while a measurement of the extra Na(24) efflux resulting from repetitive pulsing gave a charge transfer of 1.4 mucoulomb/cm(2) pulse. In sodium-containing sea water and with pulses 50-75 mv more positive than E(Na) the Na(24) efflux is about 3 times the measured charge transfer. The efflux of K(42) from a previously loaded axon into normal sea water is only 50 per cent of the measured charge transfer when the membrane is held for about 5 msec. at a potential such that there is no early current, and such pulses are at 10-20/sec. The experiments appear to confirm the suggestion that the early current during bioelectric activity is sodium but provide unsatisfactory support for the identification of the delayed but sustained current solely with potassium ions. Resting Na(+) efflux is 0.6 pmole/cm(2) sec. mmole [Na](1), while the apparent K(+) efflux is about 250 pmole/cm(2) sec. and is little affected by hyperpolarization.
Topics: Animals; Axons; Decapodiformes; Ions; Neurons; Potassium; Sodium
PubMed: 14477156
DOI: 10.1016/s0006-3495(62)86854-4 -
BMC Nephrology Jul 2016The multi-racial and multi-ethnic population of South Africa has significant variation in their nutritional habits with many black South Africans undergoing a... (Review)
Review
BACKGROUND
The multi-racial and multi-ethnic population of South Africa has significant variation in their nutritional habits with many black South Africans undergoing a nutritional transition to Western type diets. In this review, we describe our practical approaches to the dietary and nutritional management of chronic kidney disease (CKD) patients in Cape Town, South Africa.
DISCUSSION
Due to poverty and socio-economic constraints, significant challenges still exist with regard to achieving the nutritional needs and adequate dietary counselling of many CKD patients (pre-dialysis and dialysis) in South Africa. Inadequate workforce to meet the educational and counselling needs of patients, inability of many patients to effectively come to terms with changing body and metabolic needs due to ongoing kidney disease, issues of adherence to fluid and food restrictions as well as adherence to medications and in some cases the inability to obtain adequate daily food supplies make up some of these challenges. A multi-disciplinary approach (dietitians, nurses and nephrologists) of regularly reminding and educating patients on dietary (especially low protein diets) and nutritional needs is practiced. The South African Renal exchange list consisting of groups of food items with the same nutritional content has been developed as a practical tool to be used by dietitians to convert individualized nutritional prescriptions into meal plan to meet the nutritional needs of patients in South Africa. The list is currently utilized in counselling CKD patients and provides varied options for food items within the same group (exchangeable) as well as offering ease for the description of suitable meal portions (sizes) to our patients. Regular and continuous education of CKD patients by a multi-disciplinary team in South Africa enables our patients to meet their nutritional goals and retard CKD progression. The South African renal exchange list has proved to be a very useful tool in meeting this need.
Topics: Diet, Protein-Restricted; Diet, Sodium-Restricted; Food Supply; Humans; Nutritive Value; Patient Care Team; Patient Education as Topic; Phosphates; Potassium, Dietary; Renal Insufficiency, Chronic; Socioeconomic Factors; South Africa; Water-Electrolyte Balance
PubMed: 27391878
DOI: 10.1186/s12882-016-0297-4 -
The Journal of Clinical Investigation Nov 1970The effect of potassium administration and of dietary potassium deprivation on plasma renin activity and aldosterone excretion has been studied in 10 normal subjects and...
The effect of potassium administration and of dietary potassium deprivation on plasma renin activity and aldosterone excretion has been studied in 10 normal subjects and in 12 hypertensive patients maintained on a constant dietary regimen. Potassium administration reduced plasma renin activity in 18 of 28 studies of both normal and hypertensive subjects. Suppression of renin often occurred despite sodium diuresis induced by potassium administration. The renin suppression was related to induced changes in plasma potassium concentration and urinary potassium excretion. The failure of suppression of plasma renin in 10 studies could be accounted for by the smaller amounts of potassium administered to these subjects, together with a possibly overriding influence of an induced sodium diuresis. In six studies potassium deprivation invariably increased plasma renin activity even though a tendency for sodium retention often accompanied this procedure. The data indicate that both the suppression of plasma renin activity induced by potassium administration and the stimulation of renin activity which follows potassium depletion occur independently of associated changes in either aldosterone secretion or in sodium balance. However, the results do suggest that in various situations, the influence of potassium on plasma renin activity may be either amplified or preempted by changes in sodium balance. These interactions between potassium and plasma renin could be mediated by an ill-defined extrarenal pathway. But the findings are more consistent with an intrarenal action of potassium ions to modify renin release. Potassium might modify renin secretion directly by acting on the juxtaglomerular cells or by a change in its tubular reabsorption or secretion. The effects of potassium ions on renin secretion might also be mediated indirectly via an induced change in tubular sodium transport.
Topics: Adult; Aldosterone; Angiotensin II; Biological Transport, Active; Blood Pressure; Diet Therapy; Female; Humans; Hypertension; Juxtaglomerular Apparatus; Kidney; Male; Middle Aged; Natriuresis; Potassium; Potassium Deficiency; Renin; Sodium
PubMed: 4319970
DOI: 10.1172/JCI106430 -
California Medicine Nov 1953A deficiency of potassium in a patient after operation is manifest clinically by anorexia, malaise, apathy, weakness, abdominal distention and hypochloremia. Many...
A deficiency of potassium in a patient after operation is manifest clinically by anorexia, malaise, apathy, weakness, abdominal distention and hypochloremia. Many patients who have had a prolonged disturbance in nutrition may have a "subclinical" hypopotassemia. Prophylaxis by means of replacement of the potassium excreted daily in the urine is the ideal treatment. When the clinical picture of potassium deficit develops, the amount of the potassium ion needed for replacement should be calculated on the basis of the total amount of water in the body of the patient.
Topics: Acid-Base Imbalance; Body Fluids; Humans; Hypokalemia; Ions; Postoperative Care; Potassium; Potassium Deficiency; Water-Electrolyte Imbalance
PubMed: 13106717
DOI: No ID Found -
ELife May 2022Structures of the human lysosomal K channel transmembrane protein 175 (TMEM175) in open and closed states revealed a novel architecture lacking the canonical K...
Structures of the human lysosomal K channel transmembrane protein 175 (TMEM175) in open and closed states revealed a novel architecture lacking the canonical K selectivity filter motif present in previously known K channel structures. A hydrophobic constriction composed of four isoleucine residues was resolved in the pore and proposed to serve as the gate in the closed state, and to confer ion selectivity in the open state. Here, we achieve higher-resolution structures of the open and closed states and employ molecular dynamics simulations to analyze the conducting properties of the putative open state, demonstrating that it is permeable to K and, to a lesser degree, also Na. Both cations must dehydrate significantly to penetrate the narrow hydrophobic constriction, but ion flow is assisted by a favorable electrostatic field generated by the protein that spans the length of the pore. The balance of these opposing energetic factors explains why permeation is feasible, and why TMEM175 is selective for K over Na, despite the absence of the canonical selectivity filter. Accordingly, mutagenesis experiments reveal an exquisite sensitivity of the channel to perturbations that mitigate the constriction. Together, these data reveal a novel mechanism for selective permeation of ions by TMEM175 that is unlike that of other K channels.
Topics: Dehydration; Humans; Ions; Lysosomes; Molecular Dynamics Simulation; Potassium; Potassium Channels; Protein Conformation; Sodium
PubMed: 35608336
DOI: 10.7554/eLife.75122 -
Nutrients Jun 2022Using Food Frequency Questionnaires (FFQs) to compare dietary references for screening has been in high demand. However, FFQs have been widely used for ranking...
Validity of the Food Frequency Questionnaire-Estimated Intakes of Sodium, Potassium, and Sodium-to-Potassium Ratio for Screening at a Point of Absolute Intake among Middle-Aged and Older Japanese Adults.
Using Food Frequency Questionnaires (FFQs) to compare dietary references for screening has been in high demand. However, FFQs have been widely used for ranking individuals in a population based on their dietary intake. We determined the validity of sodium (salt equivalent) intake, potassium intake, and sodium-to-potassium (Na/K) ratio obtained using the FFQ for identifying individuals who deviated from the dietary reference intakes (DRIs) measured using multiple 24-h urinary excretion measurements or 12-day weighed food records (WFR). This study included 235 middle-aged subjects. The correlation coefficients (CCs) between the FFQ and WFR estimates were mostly moderate (0.24−0.54); the CCs between the FFQ and 24-h urinary excretion measurements were low or moderate (0.26−0.38). Values of area under the receiver-operating curve (AUC) at the point of DRIs for salt equivalent or potassium were >0.7 with the WFR as the reference standard and 0.60−0.76 with the 24-h urinary excretion as the reference standard. Using both standard measures, the AUC for the Na/K ratio was <0.7. The accuracy of salt equivalent and potassium intake estimation using the FFQ to determine absolute intake point was comparable to that using WFR, allowing for quantified error, but not as good as that of 24-h urinary excretion.
Topics: Adult; Aged; Diet Records; Humans; Ions; Japan; Middle Aged; Potassium; Reproducibility of Results; Sodium; Sodium Chloride, Dietary; Surveys and Questionnaires
PubMed: 35807775
DOI: 10.3390/nu14132594