Calcium-activated chloride channels (CaCC) encoded by family members of transmembrane proteins of unknown function 16 (TMEM16) have recently been intensely studied for functional properties as well ...as their physiological roles as chloride channels in various tissues. One technical hurdle in studying these channels is the well-known channel rundown that frequently impairs the precision of electrophysiological measurements for the channels. Using experimental protocols that employ fast-solution exchange, we circumvented the problem of channel rundown by normalizing the Ca(2+)-induced current to the maximally-activated current obtained within a time period in which the channel rundown was negligible. We characterized the activation of the TMEM16A-encoded CaCC (also called ANO1) by Ca(2+), Sr(2+), and Ba(2+), and discovered that Mg(2+) competes with Ca(2+) in binding to the divalent-cation binding site without activating the channel. We also studied the permeability of the ANO1 pore for various anions and found that the anion occupancy in the pore-as revealed by the permeability ratios of these anions-appeared to be inversely correlated with the apparent affinity of the ANO1 inhibition by niflumic acid (NFA). On the other hand, the NFA inhibition was neither affected by the degree of the channel activation nor influenced by the types of divalent cations used for the channel activation. These results suggest that the NFA inhibition of ANO1 is likely mediated by altering the pore function but not through changing the channel gating. Our study provides a precise characterization of ANO1 and documents factors that can affect divalent cation activation and NFA inhibition of ANO1.
Purpose
Recent data suggest that both elevated serum chloride levels and volume overload may be harmful during fluid resuscitation. The purpose of this study was to examine the relationship between ...the intravenous chloride load and in-hospital mortality among patients with systemic inflammatory response syndrome (SIRS), with and without adjustment for the crystalloid volume administered.
Methods
We conducted a retrospective analysis of 109,836 patients ≥18 years old that met criteria for SIRS and received fluid resuscitation with crystalloids. We examined the association between changes in serum chloride concentration, the administered chloride load and fluid volume, and the ‘volume-adjusted chloride load’ and in-hospital mortality.
Results
In general, increases in the serum chloride concentration were associated with increased mortality. Mortality was lowest (3.7 %) among patients with minimal increases in serum chloride concentration (0–10 mmol/L) and when the total administered chloride load was low (3.5 % among patients receiving 100–200 mmol;
P
< 0.05 versus patients receiving ≥500 mmol). After controlling for crystalloid fluid volume, mortality was lowest (2.6 %) when the volume-adjusted chloride load was 105–115 mmol/L. With adjustment for severity of illness, the odds of mortality increased (1.094, 95 % CI 1.062, 1.127) with increasing volume-adjusted chloride load (≥105 mmol/L).
Conclusions
Among patients with SIRS, a fluid resuscitation strategy employing lower chloride loads was associated with lower in-hospital mortality. This association was independent of the total fluid volume administered and remained significant after adjustment for severity of illness, supporting the hypothesis that crystalloids with lower chloride content may be preferable for managing patients with SIRS.
In this study, a new physically and chemically based model taking into account thermodynamic equilibrium, kinetics and surface complexation is proposed to predict the ingress of chloride ions into ...saturated concretes. The numerical results of this multi-ionic model are compared to experimental data such as total and free chloride concentration profiles and chloride binding isotherms. With only one set of parameters, the results show very good agreement for chloride binding isotherm of concretes with different w/b, types of binders (CEM I, CEM III, and CEM I with fly ash) and various exposure conditions (NaCl solution at different concentrations). Such a model overcomes the use of empirical chloride binding isotherms that can be difficult to asses for concretes with supplementary cementitious materials. The very good results underline the need to take into account all the physical and chemical phenomena included in the model.
Gating the Selectivity Filter in ClC Chloride Channels Dutzler, Raimund; Campbell, Ernest B.; MacKinnon, Roderick
Science (American Association for the Advancement of Science),
04/2003, Letnik:
300, Številka:
5616
Journal Article
Recenzirano
ClC channels conduct chloride (Cl-) ions across cell membranes and thereby govern the electrical activity of muscle cells and certain neurons, the transport of fluid and electrolytes across ...epithelia, and the acidification of intracellular vesicles. The structural basis of ClC channel gating was studied. Crystal structures of wild-type and mutant Escherichia coli ClC channels bound to a monoclonal Fab fragment reveal three Cl- binding sites within the 15-angstrom neck of an hourglass-shaped pore. The Cl- binding site nearest the extracellular solution can be occupied either by a Cl- ion or by a glutamate carboxyl group. Mutations of this glutamate residue in Torpedo ray ClC channels alter gating in electrophysiological assays. These findings reveal a form of gating in which the glutamate carboxyl group closes the pore by mimicking a Cl- ion.
The reactivity of the PGeP germylene 2,2’‐bis(di‐isopropylphosphanylmethyl)‐5,5’‐dimethyldipyrromethane‐1,1’‐diylgermanium(II), Ge(pyrmPiPr2)2CMe2, with late first‐row transition metal (Fe‐Zn) ...dichlorides has been investigated. All reactions led to PGeP pincer chloridogermyl complexes. The reactions with FeCl2 and CoCl2 afforded paramagnetic square planar complexes of formula MCl{κ3P,Ge,P‐GeCl(pyrmPiPr2)2CMe2} (M=Fe, Co). While the iron complex maintained an intermediate spin state (S1; μeff=3.0 μB) over the temperature range 50–380 K, the effective magnetic moment of the cobalt complex varied linearly with temperature from 1.9 μB at 10 K to 3.6 μB at 380 K, indicating a spin crossover behavior that involves S1/2 (predominant at T<180 K) and S3/2 (predominant at T>200 K) species. Both cobalt(II) species were detected by electron paramagnetic resonance at T<20 K. The reaction of Ge(pyrmPiPr2)2CMe2 with NiCl2(dme) (dme=dimethoxyethane) gave a square planar nickel(II) complex, NiCl{κ3P,Ge,P‐GeCl(pyrmPiPr2)2CMe2}, whereas the reaction with CuCl2 involved a redox process that rendered a mixture of the germanium(IV) compound GeCl2(pyrmPiPr2)2CMe2 and a binuclear copper(I) complex, Cu2{μ‐κ3P,Ge,P‐GeCl(pyrmPiPr2)2CMe2}2, whose metal atoms are in tetrahedral environments. The reaction of the germylene with ZnCl2 led to the tetrahedral derivative ZnCl{κ3P,Ge,P‐GeCl(pyrmPiPr2)2CMe2}.
Pincer ligands: Paramagnetic (M=FeII, CoII) and diamagnetic (M=NiII, CuI, ZnII) mononuclear (M=FeII, CoII, NiII, ZnII) and binuclear (M=CuI) complexes supported by a PGeP pincer chloridogermyl ligand have been prepared from reactions of a dipyrromethane‐derived PGeP germylene with the corresponding metal(II) chlorides.
There remains considerable debate over the active form of gold under operating conditions of a recently validated gold catalyst for acetylene hydrochlorination. We have performed an in situ x-ray ...absorption fine structure study of gold/carbon (Au/C) catalysts under acetylene hydrochlorination reaction conditions and show that highly active catalysts comprise single-site cationic Au entities whose activity correlates with the ratio of Au(I):Au(III) present. We demonstrate that these Au/C catalysts are supported analogs of single-site homogeneous Au catalysts and propose a mechanism, supported by computational modeling, based on a redox couple of Au(I)-Au(III) species.
Perovskite chloride, an anion conductor, is a promising candidate to be a solid electrolyte for high‐energy and sustainable chloride ion batteries (CIB). However, it suffers from poor structural ...stability at low temperature and in ambient conditions, which leads to its transformation from an ionic conductor to an insulator. Herein, a bismuth and chlorine dual doping strategy is developed to stabilize the cubic structure of CsSnCl3 in harsh environments. The as‐prepared dual‐doped CsSn0.9Bi0.1Cl3.1 material with an optimized composition maintains its cubic structure at the extremely low temperature of 213 K for 10 days and at 40% relative humidity for 50 days, while the undoped cubic material deteriorates and transforms to a monoclinic phase under these conditions in less than 1 day. Consequently, the dual doping achieves efficient chloride ion conduction that is superior to single bismuth doping due to the introduction of interstitial chlorine facilitating chloride ion transport. Importantly, the practicality of the as‐prepared solid electrolyte is demonstrated in different symmetric solid cells and by various CIBs using the organic electrode couple, a multivalent metal chloride cathode, or a new high‐voltage metal oxychloride cathode.
A bismuth and chlorine dual doping approach is developed to stabilize the cubic structure of perovskite chloride against the extremely low temperature of 213 K and ambient conditions with 40% relative humidity for a long period, thereby yielding the cubic CsSn0.9Bi0.1Cl3.1 solid electrolyte with efficient chloride ion conduction in different symmetric solid cells and various rechargeable chloride ion batteries.
The field of optogenetics uses channelrhodopsins (ChRs) for light-induced neuronal activation. However, optimized tools for cellular inhibition at moderate light levels are lacking. We found that ...replacement of E90 in the central gate of ChR with positively charged residues produces chloride-conducting ChRs (ChloCs) with only negligible cation conductance. Molecular dynamics modeling unveiled that a high-affinity Cl–-binding site had been generated near the gate. Stabilizing the open state dramatically increased the operational light sensitivity of expressing cells (slow ChloC). In CA1 pyramidal cells, ChloCs completely inhibited action potentials triggered by depolarizing current injections or synaptic stimulation. Thus, by inverting the charge of the selectivity filter, we have created a class of directly light-gated anion channels that can be used to block neuronal output in a fully reversible fashion.
Biological photosynthesis uses the energy of several visible light photons for the challenging oxidation of water, whereas chemical photocatalysis typically involves only single-photon excitation. ...Perylene bisimide is reduced by visible light photoinduced electron transfer (PET) to its stable and colored radical anion. We report here that subsequent excitation of the radical anion accumulates sufficient energy for the reduction of stable aryl chlorides giving aryl radicals, which were trapped by hydrogen atom donors or used in carbon-carbon bond formation. This consecutive PET (conPET) overcomes the current energetic limitation of visible light photoredox catalysis and allows the photocatalytic conversion of less reactive chemical bonds in organic synthesis.
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