No description available.

No description available.

The method utilizes both cation and anion concentrator columns in parallel as a preconcentration system. The preconcentrator system is loaded using a reagent delivery module operated for a specific time at a preset flow rate. Total injection volumes of 2-5 ml are routinely used. Various chromatograms are discussed along with detailed information concerning detection limits for sodium and chloride, the system operating conditions, and the solutions to other pitfalls which have arisen during the course of this work.

The phosphine crown ether, 16-(4'diphenylphosphinophenyl)-1,4,7,10,13-pentaoxa-16azacyclooctadecane (III), was synthesized using a reaction scheme beginning with n-phenyldiethanolamine and the dichloride of tetraethylene glycol, with an overall yield of 4%. Platinum and Palladium complexes of the ligand, of the form MC12L2, were synthesized as well. 13C NMR and picrate extraction data indicate III and IV (the crown-5 analog) both moderately bind sodium (14%, 15%) and potassium ions (17%, 28%). Compound V (a crown-5, triphenylphosphine-based ligand) will bind both sodium and potassium ions as well (18%, 6%). When IV is complexed to nickel carbonyl (Ni(CO)3), the addition of sodium and potassium ions cause the Al carbonyl stretching frequency to increase slightly (0.3 cm-1, 0.2 cm 1). For comparison, the addition of a proton causes the A1 carbonyl stretching frequency to increase 5.2 cm-1. However, the shift in the A1 carbonyl stretching frequency upon the addition of sodium or potassium ions indicates that ion binding by the crown ether is communicated to the phosphorus and finally to the carbonyl groups.Ball State UniversityMuncie, IN 47306 / Department of Chemistry

No description available.

Molecular dynamics simulations are an important tool for the study of biological systems, such as biomembranes. The missing electronic polarization in classical non- polarizable force fields, however, produces significant inaccuracies in the interactions of membranes with charged particles, such as ions. In this work, we implement the missing electronic polarization effects into CHARMM36 force field for phospatidylcholine lipids. This implementation is done in the mean field way by using electronic continuum correction (ECC) model. We will validate the strength of ion-membrane interactions using the electrometer concept. This concept connects the response of choline order parameters of lipid molecules with the amount of charge present in the surface of the membrane. Keywords: phosphatydylcholine, calcium ions, sodium ions, electronic continuum cor- rection, electrometer concept 1

Class of 2012 Abstract / Specific Aims: The epithelial sodium channels (ENaC) found on the apical membranes of epithelial cells including those lining the respiratory tract are the rate limiting step of the absorption of excess fluid from the airspace of the alveoli. ENaC function is modulated by the effects of various physiologic signals such as the adrenergic and purinergic pathways, in addition to other local channels which control the flow of negatively charged ions such as the cystic fibrosis transmembrane conductance regulator (CFTR). We sought to determine the influence of genetic variation on the alpha subunit of ENaC at amino acid position 663 on baseline exhaled ions and pulmonary function in patients with CF. Methods: We assessed pulmonary function ( forced vital capacity[FVC], forced expiratory volume in one second [FEV1], forced expiratory flow maximum[FEFmax]) using a Medical Graphics cardiopulmonary testing device (Minneapolis, MN). Measures of exhaled sodium (Na+) and chloride (Cl-) were obtained using exhaled breathe condensate collected on a Jaeger Ecoscreen condenser unit (Cardinal Health, Yorba Linda, CA) with Na+ quantification using an atomic absorption spectrophotometer (Analyst 100; Perkin Elmer, Norwalk, CT) and Cl- anion quantification using a Dionex AS11 HC column. Healthy n=31 (n=18[58%], 9[29%], and 4[13%] subjects; Body mass index (BMI)=23±1, 25±2, and 25±2kg/ m2 for AA, AT and TT groups respectively). CF n= 42 (n=33[79%], 7[16%], and 2[5%] subjects; BMI equals 23±7, 19±0.4, and 20±2.2kg/m2 for AA, AT and TT groups respectively). Main Results: We found that the distribution of genotypes in CF differed from healthy subjects, with the AA genotype in 80% of CF and 59% in healthy. No significant difference were demonstrated in healthy subjects between genotype groups for pulmonary function and exhaled chloride while the genotypes did differ in exhaled Na (Na=2.9±0.4, 1.7±0.3, and 3.7±1.1mmol/L for AA, AT, and TT respectively, ANOVA p=0.07). CF subjects with the AA genotype had a higher baseline exhaled Cl-, FEV1, and FEFmax than those in the AA group (Cl=0.125±0.038,0.0 27±0.007, and 0.033±0.02 mmol/L ; FEV1=71±5, 68±11, and 40±22L; FEFmax=86±4, 72±7, and 44±24L/sec; for AA, AT, and TT respectively, ANOVA p<0.05, Tukey [AA vs. TT] p<0.05) while exhaled Na+ and FVC were similar between genotypes. Conclusions: Our results suggest that CF subjects with the AA genotype of the alpha subunit of the ENaC have a higher baseline exhaled Cl- and a resulting increase in pulmonary function when compared to the overactive TT groupCF patients with the TT αENaC genotype are likely candidates for early identification and treatment with inhaled ENaC inhibitors or other modulators of this pathway in order to improve survival.

No description available.

Ion channels are fundamental molecules in the nervous system that catalyze the flux of ions across the cell membrane. There are mounting evidences suggesting that the kinetic properties of ion channels undergo activity-dependent changes in various pathophysiological conditions. Here such activity-dependent changes were studied in case of two different ion channels; the rat brain derived voltage-gated Na+ channel, rNav1.2 and the human background leak K+ channel, hTREK1 using the single channel patch-clamp technique. Our results on the voltage-gated Na+ channel (Chapter III) illustrated that sustained membrane depolarization, as seen in pathophysiological conditions like epilepsy, induced a defined non-linear variation in the unitary conductance, activation, inactivation and recovery kinetic properties of the channel. Signal processing tools attributed a pseudo-oscillatory nature to the non-linearity observed in the channel properties. Prolonged membrane depolarization also induced a “molecular memory” phenomenon, characterized by clustering of dwell time events and strong autocorrelation in the dwell time series. The persistence of such molecular memory was found to be dependent on the duration of depolarization. Similar plastic changes were observed in case of the hTREK1 channel in presence of saturating concentrations of agonist, trichloroethanol (TCE) (Chapter IV). TREK1 channel behaves similar to single enzyme molecules with a single binding site for the substrate K+ ion whereas TCE acts as an allosteric activator of the channel. We observed that with increasing concentration of TCE (10 M to 10 mM) the catalytic turnover rate exhibited progressive departure from monoexponential to multi-exponential distribution suggesting the presence of ‘dynamic disorder’ analogous to single enzyme molecules. In addition, we observed the induction of strong correlation in successive waiting times and flux intensities, exemplified by distinct mode switching between high and low flux activity, which implied the induction of memory in single ion channel. Our observation of such molecular memory in two different ion channels in different experimental conditions highlights the importance and generality of the phenomenon which is normally hidden under the ensemble behaviour of ion channels. In the final part of the work (chapter V) we observed strong negative cooperativity and half-of-sites saturation kinetics in the interaction of local anesthetic, lidocaine with hTREK1 channel. We also mapped the specific anesthetic binding site in the c-terminal domain of the channel. Further, single channel analysis and the heterodimer studies enabled us to propose a model for this interaction and provide a plausible paradigm for the inhibitory action of lidocaine on hTREK1.

[Truncated abstract] Self-filtration is here defined as particle detachment and re-deposition causing re-arrangement of the particles and therefore pore space which affects water flow in soil by decreasing hydraulic conductivity. This is of particular important in soils which are susceptible to structural breakdown. The objective of this thesis was to examine the dynamics of the self-filtration process in sodic sandy soils as affected by ionic strength and soil solution composition. The temporal changes of hydraulic conductivity and the elution of fine particles from soil columns were used as the main criteria to assess selffiltration. Two porous media exhibiting significantly different structural cohesion were examined, one a loamy sand (Balkuling soil) from agricultural land use and the second a mining residue from mineral sands operations . . . The effects of the composition of mixed calcium (Ca) and sodium (Na) ions in solution (sodium adsorption ratio (SAR)) on the exchange behaviour and saturated hydraulic conductivity were examined by carrying out batch binary exchange and saturated column transport experiments. A strong preference for Ca2+ ions in the exchange complex was observed for both soils. Generally K/Ko was found to decrease with increasing sodium adsorption ratio with the more structured Balkuling soil maintaining K/Ko for SARs 3 and 5 at an electrolyte concentration of 100 mmol/L. However measurements at the critical threshold and turbidity concentrations at a SAR of 15 revealed structural breakdown of the pore matrix system attributed to various extents of slaking, swelling, dispersion and decreases of pore radii as a result of selffiltration during leaching. These experiments illustrate the wide range of complex interactions involving clay mineralogy, solution composition and structural factors which can influence the extent of mobilization, transport and re-deposition of colloidal particles during the leaching process in soil profiles.