scholarly journals Cracking the Secret Code of the Selectivity Ratio Between K+ and Na+ Ions in the KcsA K+ Channel

Author(s):  
Yongwoon Jung ◽  
Sangyong Nam

The KcsA is a prokaryotic potassium-oriented channel, which is sourced from the Streptomyces lividans soil bacteria. From extensive studies that have been carried over the KcsA potassium channel, it has been proved that various factors enable the gating and shuttling of the potassium ions into and out of the cells. Some of the factors include the different concentration of protons in the inside and outside membrane. The other factor is the existence of the selectivity filter equipped in the exit of channel pore, which enables the movement of the K+ ions. Not only are potassium ions present in the channel but also sodium ions. Potassium and sodium ions are the ions that are essential in the conductivity of a cell because of their charge. An intuitive idea about why K+ ions are at least 10,000 times more permeant than Na+ ions is presented in various entities. The hypothesis is that the selectivity ratio is probably related to the successive entry of Na+ ions, based on the premise that the ratio seems to be relevant to unpredictable quantities caused by Brownian corrosion of ions.

Author(s):  
Yongwoon Jung

The KcsA is a prokaryotic potassium-oriented channel, which is sourced from the Streptomyces lividans soil bacteria. From extensive studies that have been carried over the KcsA potassium channel, it has been proved that various factors enable the gating and shuttling of the potassium ions into and out of the cells. Some of the factors include the different concentration of protons in the inside and outside membrane. The other factor is the existence of the selectivity filter equipped in the exit of channel pore, which enables the movement of the K+ ions. Not only are potassium ions present in the channel but also sodium ions. Potassium and sodium ions are the ions that are essential in the conductivity of a cell because of their charge. An intuitive idea about why K+ ions are at least 10,000 times more permeant than Na+ ions is presented in various entities. The hypothesis is that the selectivity ratio is probably related to the successive entry of Na+ ions, based on the premise that the ratio seems to be relevant to unpredictable quantities caused by Brownian corrosion of ions.


2020 ◽  
Vol 65 (6) ◽  
pp. 1058-1064
Author(s):  
С.В. Пастон ◽  
◽  
А.М. Поляничко ◽  
О.В. Шуленина ◽  
Д.Н. Осинникова ◽  
...  

The aqueous environment and ionic surrounding are the most important factors determining the conformation of DNA and its functioning in the cell. The specificity of the interaction between DNA and cations is especially pronounced with a decrease in water activity. In this work, we studied the B-A transition in high molecular weight DNA with a decrease of humidity in the film with different contents of Na+ ions using FTIR spectroscopy. The IR spectrum of DNA is not only very sensitive to the state of its secondary structure, but also allows us to estimate the amount of water bound to DNA. Upon dehydration of the DNA film, changes characteristic of the B-A transition were observed in the IR absorption spectrum. Using thermogravimetric analysis, it was shown that the degree of DNA hydration reaches the saturation level at a relative humidity of 60% and decreases slightly upon further drying. It has been established that with increasing Na+ concentration, the amount of water strongly bound to DNA decreases. Along with it, sodium ions destroy the hydration shell of DNA and are able to interact directly with phosphate groups.


2021 ◽  
Vol 22 (6) ◽  
pp. 2999
Author(s):  
Benjamin J. Buckley ◽  
Ashna Kumar ◽  
Ashraf Aboelela ◽  
Richard S. Bujaroski ◽  
Xiuju Li ◽  
...  

The K+-sparing diuretic amiloride shows off-target anti-cancer effects in multiple rodent models. These effects arise from the inhibition of two distinct cancer targets: the trypsin-like serine protease urokinase-type plasminogen activator (uPA), a cell-surface mediator of matrix degradation and tumor cell invasiveness, and the sodium-hydrogen exchanger isoform-1 (NHE1), a central regulator of transmembrane pH that supports carcinogenic progression. In this study, we co‑screened our library of 5- and 6-substituted amilorides against these two targets, aiming to identify single-target selective and dual-targeting inhibitors for use as complementary pharmacological probes. Closely related analogs substituted at the 6-position with pyrimidines were identified as dual-targeting (pyrimidine 24 uPA IC50 = 175 nM, NHE1 IC50 = 266 nM, uPA selectivity ratio = 1.5) and uPA-selective (methoxypyrimidine 26 uPA IC50 = 86 nM, NHE1 IC50 = 12,290 nM, uPA selectivity ratio = 143) inhibitors, while high NHE1 potency and selectivity was seen with 5-morpholino (29 NHE1 IC50 = 129 nM, uPA IC50 = 10,949 nM; NHE1 selectivity ratio = 85) and 5-(1,4-oxazepine) (30 NHE1 IC50 = 85 nM, uPA IC50 = 5,715 nM; NHE1 selectivity ratio = 67) analogs. Together, these amilorides comprise a new toolkit of chemotype-matched, non-cytotoxic probes for dissecting the pharmacological effects of selective uPA and NHE1 inhibition versus dual-uPA/NHE1 inhibition.


1961 ◽  
Vol 38 (2) ◽  
pp. 315-322
Author(s):  
J. E. TREHERNE

1. The influx of sodium and potassium ions into the central nervous system of Periplaneta americana has been studied by measuring the increase in radioactivity within the abdominal nerve cord following the injection of 24NA and 42K. into the haemolymph. 2. The calculated influx of sodium ions was approximately 320 mM./l. of nerve cord water/hr. and of potassium ions was 312 mM./l. of nerve cord water/hr. These values are very approximately equivalent to an influx per unit area of nerve cord surface of 13.9 x 10-2 M cm. -2 sec.-1 for sodium and 13.5 x 10-12 M cm. -2 sec.-1 for potassium ions. 3. The relatively rapid influxes of these ions are discussed in relation to the postulated function of the nerve sheath as a diffusion barrier. It is suggested that a dynamic steady state rather than a static impermeability must exist across the sheath surrounding the central nervous system in this insect.


Author(s):  
Majd Almakhatreh ◽  
Ezar Hafez ◽  
Ehab Tousson ◽  
Ahmed Masoud

Aims: Etoposide (Vepesid) is chemotherapeutic drugs that inhibit topoisomerase II activity and long been used for treatment of human malignancies, where it is a semi-synthetic compound derived from the plant Podophyllum peltatum. The current study was designed to investigate the possible protective effect of rosemary extract against Etoposide -induced changes in liver and kidney functions, and DNA damage in rats. Materials and Methods: A total of 50 male Wistar albino rats were divided randomly into four groups (1st group was control; 2nd group was treated with rosemary, 3rd group was received etoposide, and 4th & 5th groups was co- and post treated groups respectively). Results: The administration of Etoposide revealed a significant increase in serum ALT, AST, ALP, creatinine, urea, potassium ions, chloride ions, and DNA damage. In contrast; a significant decrease in albumen, total proteins, sodium ions, and calcium ions were when compared with control group. This increased in ALT, AST, ALP, creatinine, urea, potassium ions, chloride ions, and DNA damage was reduced after administration of rosemary when co-treated with etoposide (G4), or post-treated after etoposide  (G5) for four weeks with lowest damage in G4. Also, this decreased in albumen, total proteins, sodium ions, and calcium ions was increased after administration of rosemary when co-treated with etoposide (G4), or post-treated after etoposide (G5) for four weeks with lowest damage in G4. Conclusion: It could be concluded that rosemary has a promising role and it worth to be considered as a natural substance for protective the liver and kidney toxicity induced by etoposide (Vepesid) chemotherapy.


1963 ◽  
Vol 204 (2) ◽  
pp. 257-261 ◽  
Author(s):  
Edwin M. Uyeki

The intracellular distribution of several cell constituents was studied at different periods after partial hepatectomy in the rat. The temporal pattern of cation and protein distribution can be divided into two phases: there is an initial phase in the first 24 hr posthepatectomy in which sodium and water increased in tissues concomitant with a decrease in potassium and protein. The levels of these several constituents subsequently approached values that were higher than in the control at 1 and 2 days posthepatectomy and were generally maintained at these values throughout the assay period. The reasons for the accumulation of higher than normal levels of both potassium and sodium are as yet uninterpreted; the higher than control potassium-to-sodium ratios generally observed in the intracellular compartments are due to the relative greater accumulation of potassium ions over sodium ions during this period. Comparing the intracellular compartments, the greatest alterations of constituents in the early phases of liver regeneration were observed in the soluble portion.


1978 ◽  
Vol 12 (1) ◽  
pp. 37-39 ◽  
Author(s):  
M. Macari ◽  
C. R. Machado

Semen was collected weekly from New Zealand white rabbits from the 1st positive mounting test to 43 weeks of age by means of an artificial vagina. The mean values of the results obtained in the 1st and 20th collection weeks were respectively: volume (ml) 0·61 ± 0·30 and 0·70 ± 0·19; pH 7·22 ± 0·50 and 7·19 ± 0±15; concentration (sperm/mm3 x 103) 750 ± 207 and 381 ± 90; fructose (mg/l00 ml) 117 ± 58 and 203 ± 121; citric acid (mg/l00 ml) 256 ± 90 and 200 ± 97; sodium ions (mEq/l) 133 ± 31 and 163 ± 46; potassium ions (mEq/l) 40 ± 21 and 29 ± 14. On the basis of these results, New Zealand white rabbits reach sexual maturity by 6 months of age.


1969 ◽  
Vol 54 (1) ◽  
pp. 306-326 ◽  
Author(s):  
R. L. Post ◽  
S. Kume ◽  
T. Tobin ◽  
B. Orcutt ◽  
A. K. Sen

In plasma membranes of intact cells an enzymatic pump actively transports sodium ions inward and potassium ions outward. In preparations of broken membranes it appears as an adenosine triphosphatase dependent on magnesium, sodium, and potassium ions together. In this adenosine triphosphatase a phosphorylated intermediate is formed from adenosine triphosphate in the presence of sodium ions and is hydrolyzed with the addition of potassium ions. The normal intermediate was not split by adenosine diphosphate. However, selective poisoning by N-ethylmaleimide or partial inhibition by a low magnesium ion concentration yielded an intermediate split by adenosine diphosphate and insensitive to potassium ions. Pulse experiments on the native enzyme supported further a hypothesis of a sequence of phosphorylated forms, the first being made reversibly from adenosine triphosphate in the presence of sodium ion and the second being made irreversiblyfrom the first and hydrolyzed in the presence of potassium ion. The cardioactive steriod inhibitor, ouabain, appeared to combine preferentially with the second form. Phosphorylation was at the same active site according to electrophoretic patterns of proteolytic phosphorylated fragments of both reactive forms. It is concluded that there is a conformational change in the active center for phosphorylation during the normal reaction sequence. This change may be linked to one required theoretically for active translocation of ions across the cell membrane.


1982 ◽  
Vol 216 (1203) ◽  
pp. 225-251 ◽  

(i) Effects of extracellular sodium concentration, [Na] o , on endplate channel characteristics were investigated in voltage-clamped, glycerol- treated toad sartorius fibres. (ii) The relation between [Na] o (and [K] o ) and acetylcholine null potential could be reasonably well fitted by the Goldman-Hodgkin-Katz type of equation, except when [Na] o was higher than normal. Anions had no significant effect on the null potential. (iii) Endplate channel open time (ז), whether measured from miniature endplate currents or from current fluctuations induced by iontophoresis of acetylcholine, varied inversely with [Na] o . The relation between ז -1 (=α) and [Na] o could be fitted by α = αmax [Na] o / ( K m +|[Na] o ) with a K m of 92 mM. (iv) Endplate conductance, measured at the peak of endplate currents or at the peak of spontaneous miniature endplate currents, increased nonlinearly with [Na] o . (v) Single channel conductance, γ, also increased nonlinearly with [Na] o . Experimental observations at -90 mV could be fitted by the relation γ = γ max [Na] o / ( K m + [Na] o ), giving values for γ max and K m of 47 pS and 146 mM respectively. Correcting channel conductance for the contribution from potassium ions gave values of γmax and K m of 78 pS and 423 mM respectively. (vi) The results are consistent with the hypothesis that binding sites for Na ions can modulate both channel lifetime and conductance and that these sites become saturated at higher sodium concentrations.


Sign in / Sign up

Export Citation Format

Share Document