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At least 811 records · Page 45Linked to original sources
PubMed1986

The anion specificity of the sodium-potassium-chloride cotransporter in rabbit kidney outer medulla: studies on medullary plasma membranes.

Plasma membrane vesicles were isolated from rabbit kidney outer medulla and employed in sodium, rubidium, and chloride flux studies. Chloride dependence and bumetanide sensitivity of (part of) the sodium and rubidium flux indicate that this plasma membrane fraction can be used to study the properties of Na-K-2Cl cotransport system present in the luminal membrane of the medullary thick ascending limb. The anion specificity of the cotransporter was investigated by determining the effect of anion replacement on sodium fluxes. When chloride was completely replaced by bromide, iodide, nitrate, or thiocyanate only bromide could effectively substitute for chloride (90% activity), whereas sodium uptake in the presence of iodide, nitrate, and thiocyanate amounted to only 25% of the sodium uptake observed in the presence of chloride. When similar replacement experiments were performed in the presence of 10 mmol/l chloride, bromide could substitute for chloride by 110%, iodide and nitrate by 60%, and thiocyanate by 70%. In the presence of 10 mmol/l bromide iodide, nitrate, and thiocyanate were similarly effective. The effect of nitrate and chloride on sodium flux was additive. Bumetanide-sensitive chloride uptake was inhibited by nitrate, the inhibition was however only partly, amounting to 60%. The results obtained are compatible with the view that the two anion binding sites of the Na-K-2Cl cotransporter can exhibit a different substrate specificity and that the transporter in addition to a 2Cl mode can also operate in a 2Br, Cl-, A- and Br-, A- mode, A- representing iodide, nitrate, or thiocyanate.

Animals↗
PubMed1992

The functional, oxygen-linked chloride binding sites of hemoglobin are contiguous within a channel in the central cavity.

Chloride ion is a major allosteric regulator for many hemoglobins and particularly for bovine hemoglobin. A site-directed reagent for amino groups, methyl acetyl phosphate, when used for global rather than selective modification of R (oxy) and T (deoxy) state bovine hemoglobin, can acetylate those functional amino groups involved in binding of chloride; the extensively acetylated hemoglobin tetramer retains nearly full cooperativity. The chloride-induced decrease in the oxygen affinity parallels the acetylation of bovine hemoglobin (i.e., their effects are mutually exclusive), suggesting that methyl acetyl phosphate is a good probe for the functional chloride binding sites in hemoglobins. Studies on the overall alkaline Bohr effect indicates that the part of the contribution dependent on chloride and reduced by 60% after acetylation is due to amino groups, Val-1(alpha) and Lys-81(beta); the remaining 40% is contributed by the imidazole side chain of His-146(beta), which is not acetylated by methyl acetyl phosphate, and is not dependent on chloride. The five amino groups--Val-1(alpha), Lys-99(alpha), Met-1(beta), Lys-81(beta), and Lys-103(beta)--of bovine hemoglobin that are acetylated in an oxygen-linked fashion are considered functional chloride binding sites. Molecular modeling indicates that these functional chloride binding sites are contiguous from one end of the central cavity of hemoglobin to the other; some of them are aligned within a chloride channel connecting each end of the dyad axis.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetylation↗
PubMed1988

On the mechanism by which chloride corrects metabolic alkalosis in man.

To determine whether administration of chloride corrects chloride-depletion metabolic alkalosis (CDA) by correction of plasma volume contraction and restoration of glomerular filtration rate or by an independent effect of chloride repletion, CDA was produced in normal men by the administration of furosemide and maintained by restriction of dietary sodium chloride intake. Negative sodium balance (-112 +/- 16 meq) and reduced plasma volume (2.53 versus 2.93 liters, p less than 0.05) developed. The cumulative chloride deficit of 271 +/- 16 meq was then repleted by oral potassium chloride (267 +/- 19 meq) over 36 hours with continued serial measurements of glomerular filtration rate, effective renal plasma flow, plasma volume, body weight, and plasma renin and aldosterone levels. CDA was corrected, even though body weight, plasma volume, glomerular filtration rate, and renal plasma flow all remained reduced and plasma aldosterone was elevated; urinary bicarbonate excretion increased during correction. Administration of an identical potassium chloride load to similarly sodium-depleted but not chloride-depleted normal subjects produced no change in acid-base status. It is concluded that chloride repletion can correct CDA by a renal mechanism without restoring plasma volume or glomerular filtration rate or by altering sodium avidity.

Adult↗
PubMed2004

Involvement of chloride channels in hepatic copper metabolism: ClC-4 promotes copper incorporation into ceruloplasmin.

BACKGROUND & AIMS: Copper transport in hepatocytes is regulated by the interaction of multiple pumps, chaperones, and accessory proteins. Intracellular chloride channels are essential for copper metabolism in yeast but their role in Cu transport in hepatocytes is unknown. The aim of this study was to determine whether chloride channels are modulators of copper incorporation into ceruloplasmin (CP). METHODS: The effects of chloride concentration and chloride channel expression on secretion of holoCp and apoCp was measured by gel electrophoresis and immunoblotting. ClC family chloride channel expression in hepatocytes was determined by Western blotting. The association of ClC-4 and the Wilson's disease protein (ATP7B) was determined by co-immunoprecipitation. RESULTS: Chloride substitution reduced total Cp secretion and the ratio of secreted holoCp to apoCp (P = 0.038). The role of specific chloride channels was examined by cotransfection of ceruloplasmin and the chloride channel. Overexpression of ClC-4 doubled copper incorporation into ceruloplasmin (P = 0.011), whereas identical overexpression of ClC-3 had no effect. The effect of ClC-4 was most pronounced under copper-limiting conditions in which it increased copper incorporation more than 4-fold (P = 0.037). ClC-4 protein was abundant in hepatocyte membranes and was localized in intracellular vesicles containing ATP7B. CONCLUSIONS: ClC-4 is an intracellular chloride channel that stimulates copper incorporation into ceruloplasmin, probably by improving the efficiency of the ATP7B copper pump. It is thus an important component of the regulation of hepatic copper transport and may modulate Cu transport rates during copper deficiency, Wilson's disease, and other copper toxicosis syndromes.

Adenosine Triphosphatases↗
PubMed2002

The calcium-dependent chloride conductance mediator pCLCA1.

The regulatory behavior, inhibitor sensitivity, and properties of the whole cell chloride conductance observed in cells expressing the cDNA coding for a chloride conductance mediator isoform of the CLCA gene family, pCLCA1, have been studied. Common C-kinase consensus phosphorylation sites between pCLCA1 and the closely related human isoform hCLCA1 are consistent with a role for calcium in channel activation. Both channels are activated rapidly on exposure to the calcium ionophore ionomycin. Direct involvement of calcium in the activation of pCLCA1 was supported by the finding that treatment with the intracellular calcium chelator 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid-AM reduced the rate of chloride efflux from NIH/3T3 cells expressing the pCLCA1 channel. No combination of A-kinase activators used was effective in activating chloride efflux via this channel despite the presence of a unique strong A-kinase consensus site in pCLCA1. Notable differences of pCLCA1 from the reported properties of CLCA family members include the failure of phorbol 12-myristate 13-acetate to activate chloride efflux in cells expressing pCLCA1 and a lack of inhibition of chloride efflux from these cells after treatment with DIDS or dithiothreitol. However, selected inhibitors of anionic conductance inhibited pCLCA1-dependent anion efflux. The electrogenic nature of the ionomycin-dependent efflux of chloride from cells expressing pCLCA1 was confirmed by detection of outwardly rectifying chloride current and inhibition of this current by chloride conductance inhibitors in a whole cell patch-clamp study.

3T3 Cells↗
PubMed2000

Expression of the chloride channel ClC-2 in the murine small intestine epithelium.

The chloride channel ClC-2 has been implicated in neonatal airway chloride secretion. To assess its role in secretion by the small intestine, we assessed its subcellular expression in ileal segments obtained from mice and studied the chloride transport properties of this tissue. Chloride secretion across the mucosa of murine ileal segments was assessed in Ussing chambers as negative short-circuit current (I(sc)). If ClC-2 contributed to chloride secretion, we predicted on the basis of previous studies that negative I(sc) would be stimulated by dilution of the mucosal bath and that this response would depend on chloride ion and would be blocked by the chloride channel blocker 5-nitro-2-(3-phenylpropylamino) benzoic acid but not by DIDS. In fact, mucosal hypotonicity did stimulate a chloride-dependent change in I(sc) that exhibited pharmacological properties consistent with those of ClC-2. This secretory response is unlikely to be mediated by the cystic fibrosis transmembrane conductance regulator (CFTR) channel because it was also observed in CFTR knockout animals. Assessment of the native expression pattern of ClC-2 protein in the murine intestinal epithelium by confocal and electron microscopy showed that ClC-2 exhibits a novel distribution, a distribution pattern somewhat unexpected for a channel involved in chloride secretion. Immunolabeled ClC-2 was detected predominantly at the tight junction complex between adjacent intestinal epithelial cells.

4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid↗
PubMed1986

Stoichiometry of sodium chloride transport by rectal gland of Squalus acanthias.

The stoichiometry of the sodium chloride cotransport system was examined in isolated perfused rectal glands of Squalus acanthias by kinetic analysis of the effect on chloride secretion of progressive substitutions of other ions for sodium and chloride in the perfusate. Secretion was stimulated by a constant infusion of dibutyryl cyclic AMP (5 X 10(-5) M) and theophylline (2.5 X 10(-4) M). Sodium was replaced by N-methyl-D-glucamine, whereas chloride was replaced by gluconate. The Km values for sodium, obtained using three different graphic methods, were close to or at the normal concentration of sodium in the plasma of the shark, suggesting that plasma sodium concentration regulates transport by the gland. The Km values for chloride were far below the normal concentration of chloride in the plasma, indicating that the chloride sites are normally saturated and therefore plasma chloride concentration cannot control transport by the gland. Hill plots revealed slopes of 1.06 for sodium and 1.6 for chloride, consistent with the hypothesis that 2 Cl- and 1 Na+ interact in the cotransport process. The cotransport linkage of 2 Cl- with 1 Na+ in the initial step of entry into the cell can be viewed as a device that doubles the energetic efficiency of salt transport, allowing 2 NaCl to be secreted for every 1 Na+ actively pumped.

Animals↗
PubMed1979

Effect of a low chloride diet on lactating Holstein cows.

Twenty primiparous lactating Holstein cows were fed diets supplemented with either .5% sodium chloride or .75% sodium bicarbonate. Those fed the latter diet conserved chloride by reducing the chloride concentration in urine, feces, and, to a small but nonsignificant amount, in milk. The low chloride diet did not affect consumption of feed dry matter and water or milk production and composition. There was no indication of pica or other aberrant taste behavior. One half of the cows in each diet group was given free choice salt block of trace elements. Those fed the low chloride diet consumed more salt (337 versus 149 g/cow per wk). When chloride requirements have been established and data on chloride composition become more widely available, it will be possible to include both sodium and chloride in diet formulations and omit salt. This will reduce the amount of salt needed as either a sodium or chloride supplement.

Animal Feed↗
PubMed2000

Chloride channel expression in cultured human fetal RPE cells: response to oxidative stress.

PURPOSE: The human fetal cell line RPE 28 SV4 has been useful for studies of oxidative stress and apoptosis in retinal pigmented epithelium. This cell model is now assessed in functional investigations of chloride channel activity. The study aims to determine the presence of specific chloride channels, including CFTR and ClC channels, to identify the properties of membrane chloride currents and to assess their modulation by hydrogen peroxide, cAMP, and other agents. METHODS: Channel expression was determined using RT-PCR and cDNA cloning and biochemical and immunocytochemical methods. Membrane currents were analyzed using whole-cell, patch-clamp techniques. RESULTS: RT-PCR results confirmed the presence of ClC-5 mRNA, and a full-length clone encoding ClC-3 was isolated from a cDNA library for RPE 28 SV4 cells. Specific staining for CFTR and several ClC channels was detected by immunocytochemistry. Whole-cell chloride currents (under conditions of symmetrical chloride concentrations) averaged 16.9 +/- 3.4 pA/pF (at +100 mV; n = 8), showed outward rectification, and had an anion permeability sequence of Cl(-) > I(-) > cyclamate. Currents were stimulated by cAMP cocktail (250 microM cAMP, 100 microM IBMX, and 25 microM forskolin) and were inhibited by 1 mM DIDS. The oxidative agent hydrogen peroxide (100 microM) decreased the current by 34% +/- 10% (n = 4). CONCLUSIONS. These findings suggest that RPE 28 SV4 cells possess regulated chloride channels including CFTR and members of the ClC chloride channel family. The inhibition of chloride currents by H(2)O(2) suggests that this cell line may be advantageous for studies of chloride channel modulation by oxidative stress.

1-Methyl-3-isobutylxanthine↗
PubMed1995

Effect of chloride on the binding kinetics of various stilbenedisulfonates to band 3.

To determine the mechanism of apparent competitive binding of chloride and stilbenedisulfonates ( S ) to band 3 ( B ), we have compared the binding kinetics of three stilbenedisulfonates [ DIDS, 4,4'-diisothiocyanato-2, 2'-stilbenedisulfonate; H2DIDS 4,4'-diisothiocyanodihydro-2, 2'-stilbenedisulfonate and DBDS, 4,4'-dibenzamido-2, 2'-stilbenedisulfonate ] in the absence and presence of 150 mM sodium chloride at constant ionic strength. Biphasic time courses were observed with the fast phase rate constants following second-order kinetics, and the slow phase rate constants following saturation kinetics according to the mechanism: [formula: see text] The results can be understood in terms of the effect of chloride on each of these reaction steps. Chloride increased k1 by about 2-fold, but decreased k-1 8-fold for H2DIDS. Thus, 150 mM chloride increased the initial affinity of H2DIDS by about 19-fold. There was a 3-fold increase in the initial affinity for DIDS, but little or no effect of chloride on the initial affinity of DBDS. There was no effect of chloride on k2, but, previous "off" rate measurements showed that 150 mM chloride increases k-2 about 16-fold for DBDS and about 12-fold for H2DIDS. Taken together, these results indicate that chloride allosterically competes with stilbenedisulfonates for binding to band 3, predominantly by substantially shifting the second isomerization equilibrium to the left.

4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid↗
PubMed1997

Chloride channels: an emerging molecular picture.

Chloride channels are probably found in every cell, from bacteria to mammals. Their physiological tasks range from cell volume regulation to stabilization of the membrane potential, signal transduction, transepithelial transport and acidification of intracellular organelles. These different functions require the presence of many distinct chloride channels, which are differentially expressed and regulated by various stimuli. These include various intracellular messengers (like calcium and cyclic AMP), pH, extracellular ligands and transmembrane voltage. Three major structural classes of chloride channels are known to date, but there may be others not yet identified. After an overview of the general functions of chloride channels, this review will focus on these cloned chloride channels: the CLC chloride channel family, which includes voltage-gated chloride channels, and the cystic fibrosis transmembrane regulator (CFTR), which performs other functions in addition to being a chloride channel. Finally, a short section deals with GABA and glycine receptors. Diseases resulting from chloride channel defects will be specially emphasized, together with the somewhat limited information about how these proteins work at the molecular level.

Animals↗
PubMed2003

The utility of tolonium chloride rinse in the diagnosis of recurrent or second primary cancers in patients with prior upper aerodigestive tract cancer.

BACKGROUND: The clinical utility of tolonium chloride rinse was compared with unaided visual examination alone in the diagnosis of oral carcinoma in patients previously treated for carcinoma of the upper aerodigestive tract. METHODS: A total of 668 patients were enrolled in this multicenter study. At each site, an oral clinical visual examination was completed by one investigator followed by tolonium chloride rinse and examination by a second investigator blinded to the examination findings of the first investigator. If a lesion was considered suspicious (urgent biopsy required at the first visit), the lesion was biopsied after tolonium chloride rinsing. Patients with lesions characterized at the first visit as not suspicious (biopsy not urgent) or that stained with tolonium chloride were asked to return for a second visit. At the second visit, any residual lesion or lesions that retained tolonium chloride were biopsied. RESULTS: A total of 96 biopsies was performed in 81 of the 668 patients (12.1%), of which 30 (31.3%) were diagnosed histologically as carcinoma/carcinoma in situ (CIS) and the remainder as inflammation (31.3%), keratosis (26.6%), dysplasia (21.9%), ulcer (2.1%), other (3.1%), or no abnormality (1.0%). Of the 30 lesions with the diagnosis of carcinoma/CIS, 12 (sensitivity 40.0%) were considered to be clinically suspicious (CS+), whereas 29 (sensitivity 96.7%) retained tolonium chloride (p =.0002). The predictive values of a positive test for clinical examination and tolonium chloride staining were similar (36.4% vs 32.6%; p =.5871), indicating that the greater sensitivity of tolonium chloride was not associated with an excessive number of unnecessary biopsies (false positives). CONCLUSIONS: Tolonium chloride rinse is more sensitive than clinical examination alone in detecting lesions that might be found on biopsy to be carcinoma or CIS. The increased sensitivity is largely attributed to lesions that stain but were not detected clinically on visual examination.

Aged↗
PubMed1977

Chloride-stimulated sulfate efflux in Ehrlich ascites tumor cells: evidence for 1:1 coupling.

The kinetics of Cl-SO4-(2) exchange in Ehrlich ascites tumor cells was investigated in an attempt to determine the stoichiometry of this process. When tumor cells, equilibrated in Cl--free, 25 mM SO4-(2) medium are placed in SO4-(2)-free, 25 mm Cl-medium, both the net amount and rate of Cl-uptake far exceeds SO4-(2) loss.. Addition of the anion transport inhibitor SITS (4-acetamido-4,-isothiocyano-stilbene-2,2'-disulfonic acid) greatly reduces sulfate efflux (97%), but has no measurable effect on chloride uptake. Addition of furosemide, a Cl-transport inhibitor, reduces chloride uptake 94% but is without effect on sulfate efflux. These findings suggest that a chloride permeability pathway exists distinct from that utilized by SO4-(2). SITS, when added to furosemide treated cells, further reduces chloride uptake as well as inhibiting sulfate efflux, and under these experimental conditions, a linear relationship exists between SITS-sensitive, net chloride uptake and sulfate loss. The slope of this line is 1.05 (correlation coefficient = 0.996) which suggests the stoichiometry of Cl-SO4-(2) exchange is 1:1. Assuming a 1:1 stoichiometry, measurement of the initial chloride influx and initial sulfate efflux indicate that 92% of net chloride uptake is independent of sulfate efflux. Taken altogether, these results support the contention that the tumor cell possesses a permeability pathway which facilitates the exchange of one sulfate for one chloride. Under conditions where anion transport is not inhibited, this coupling is obscured by a second and quantitatively more important pathway for chloride uptake. This pathway is SITS-insensitive, although partially inhibited by furosemide.

Animals↗
PubMed1995

Chloride-bicarbonate exchange through the human red cell ghost membrane monitored by the fluorescent probe 6-methoxy-N-(3-sulfopropyl)quinolinium.

The exchange of chloride and bicarbonate across the human red cell membrane has been characterized by quenching of an intracellular fluorophore, 6-methoxy-N-(3-sulfopropyl)quinolinium (SPQ). In 20 mM Hepes, pH 7.4, and varying concentrations of chloride and bicarbonate with total anion concentration of 150 mM, SPQ is quenched dynamically by chloride with an apparent Stern-Volmer quenching constant 0.071 +/- 0.016 mM-1 at 25 degrees C. Hepes alone quenched SPQ fluorescence with a quenching constant of 0.030 +/- 0.003 mM-1. Stopped-flow kinetic experiments give fluorescence time courses that, when corrected for Stern-Volmer quenching, are first order. Disulfonic stilbenes (inhibitors of anion exchange) decrease the rate of fluorescence equilibration. Transport of bicarbonate via hydration-dehydration of CO2 does not contribute to the observed kinetics. The chloride-bicarbonate exchange rate is independent of the anion concentration gradient, but increases at 25 degrees C from 1 to 4 s-1 as equilibrium chloride concentration increases from 20 to 130 mM (with concomitant decrease in bicarbonate concentration from 130 to 20 mM). The data indicate that the translocation rate of the chloride-loaded transport protein is greater than that of bicarbonate-loaded transport protein and that bicarbonate has a higher affinity for the transport protein than chloride. Our results validate the use of SPQ to measure quantitatively chloride-bicarbonate exchange in red cell ghosts. The methods we describe should be applicable to other systems exhibiting chloride-bicarbonate exchange.

Anions↗
PubMed1980

Binding kinetics of vinyl chloride and vinyl bromide at very low doses.

Vinyl chloride and vinyl bromide are metabolically activated by liver microsomal enzymes to intermediates that covalently bind to proteins and nucleic acids. Several lines of evidence suggest the involvement of the epoxides, i.e., chloroethylene oxide or bromoethylene oxide. Proven targets for alkylation are adenine, cytosine and guanine moieties in nucleic acids, and sulfhydryl groups of proteins. For all the halogenated ethylenes studied so far, including vinyl chloride and vinyl bromide, metabolism in vivo is a dose-dependent, saturable process. The metabolic capacity of rats is saturated at atmospheric concentrations of 250 ppm vinyl chloride and 55 ppm vinyl bromide. As recent reports describe a diminishment of hepatocellular glutathione in rats after exposure to vinyl chloride concentrations of 50 ppm and more, we carried out a series of experiments measuring covalent binding of vinyl chloride metabolites after exposure to different concentrations of 14C-vinyl chloride. In all of these experiments, including one of an exposure to only 2 ppm vinyl chloride, hepatic covalent protein binding was related to the dose of vinyl chloride which was actually metabolized, and the ratio between bound and metabolized material was constant. This strongly suggests that hepatic glutathione levels must have only a very limited impact on covalent protein binding of vinyl chloride metabolites, an assumption which is supported by a lacking effect of a pretreatment with diethylmaleate. A scheme of hepatocellular compartimentation of metabolic steps is proposed which serves to explain these findings.

Alkylation↗
PubMed1979

Vinyl chloride and trichloroethylene: comparison of alkylating effects of metabolites and induction of preneoplastic enzyme deficiencies in rat liver.

[1,2-14C] Vinyl chloride and [1,2-14C] trichloroethylene were incubated with rat liver microsomes, NADPH and RNA (from yeast). Whereas trichloroethylene metabolites were irreversibly bound to proteins in microsomal incubations to a higher extent than vinyl chloride metabolites, irreversible binding to RNA was lower for trichloroethylene metabolites. Hydrolysis of the RNA which was reisolated from microsomal incubations with 14C-vinyl chloride or 14C-trichloroethylene and separation of the nucleosides showed different alkylation products arising from vinyl chloride and from trichloroethylene, characteristic for vinyl chloride being formation of 1,N6-ethenoadenosine and 3,N4-enthenocytidine. The different reactivities of metabolites of vinyl chloride and of trichloroethylene prompted a comparison of the oncogenic effects of both compounds against the rat liver cell. Newborn rats were exposed for 10 weeks to 2000 ppm vinyl chloride or trichloroethylene (8 h/day; 5 days/week). After this period livers of the animals were stained for nucleoside-5-triphosphatase. Whereas the vinyl chloride exposed rats showed focal hepatocellular deficiencies in this enzyme, which are supposed to represent an early sign of malignancy, no such changes were induced by trichloroethylene exposure. The data therefore suggest differences between the hepatocarcinogenic activity of vinyl chloride and possible effects of trichloroethylene on the liver.

Adenosine↗
PubMed1990

Effects of GABA antagonists, SR 95531 and bicuculline, on GABAA receptor-regulated chloride flux in rat cortical synaptoneurosomes.

Synaptoneurosomes isolated from cerebral cortices of male Sprague-Dawley rats were used for studying GABAA receptor-regulated chloride influx. The in vitro effects of GABA antagonists, SR 95531 (a pyridazinyl GABA derivative) and bicuculline, on pentobarbital-stimulated, muscimol-stimulated or flunitrazepam-enhanced, muscimol-stimulated chloride uptake were studied. The chloride uptake was determined at 30 degrees C, for 5 sec. Pentobarbital and muscimol produced a maximal stimulation of chloride uptake in cortical synaptoneurosomes at 500 microM and 50 microMs, respectively. SR 95531 as well as bicuculline had no effect on the basal uptake of chloride. Whereas, SR 95531 (0.3 - 30 microM) and bicuculline (0.1 - 100 microM), when added 5 min before muscimol (50 microM), produced a significant concentration-dependent inhibition of muscimol (50 microM)-stimulated chloride uptake (IC50S of 0.89 +/- 0.11 microM and 13.45 +/- 2.10 microM, respectively). In studies of the inhibitory effects of SR 95531 and bicuculline on pentobarbital (500 microM)-stimulated chloride uptake, the IC50S were 0.81 +/- 0.12 microM and 3.86 +/- 1.14 microM, respectively. SR 95531 exhibited a more potent inhibitory effect than bicuculline on flunitrazepam-enhanced, muscimol-stimulated chloride uptake. The results revealed that SR 95531 has a more potent antagonistic effect than bicuculline on GABAA-regulated chloride flux.

Animals↗
PubMed1984

Intracellular chloride activity in the extensor digitorum longus (EDL) muscle of the rat.

Measurement of intracellular chloride activity in the extensor digitorum longus (EDL) muscle of the rat using liquid ion-exchanger microelectrodes gave an apparent resting value of 10 to 11 mmol liter-1. If chloride ions were distributed passively across the muscle fiber membrane the predicted value would be 4 mmol liter-1. In experiments in which the bathing fluid was changed by (a) reduction of external chloride, or incubation at low external chloride followed by a return to normal concentrations, (b) an increase or reduction in external potassium, (c) alteration in potassium and chloride in the bathing medium so as to maintain a constant [K] X [Cl] product, or in other experiments in which the membrane potential was caused to change by anoxia, or by addition of ouabain to the medium, changes in intracellular chloride activity were invariably consistent with the hypothesis that this ion is passively distributed. Measurements of intracellular chloride activity with recessed-tip solid-state Ag/AgCl electrodes gave a value of 4.6 mmol liter-1. Since the liquid ion-exchanger is known to be poorly selective for chloride, it is concluded that the chloride ion is passively distributed in rat EDL muscle.

Animals↗