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PubMed1992

[Effect of methylrosanilinium chloride to MRSA nasal carriers].

Since the end of 1987, we have noticed an increasing incidence of Methicillin resistant Staphylococcus aureus (MRSA) among the inpatients of Yamanashi Medical College Hospital. MRSA strains were identified in 70-80 percent of the specimens obtained from patients with Staphylococcus aureus. From 1988 we performed yearly bacteriological examinations of the nares of medical personnel at Yamanashi Medical College Hospital. We treated nasal carriers with OFLX drop lotion or Povidone-iodine applied to the nares. In 1991 we treated eight nasal carriers, who had been unsuccessfully treated with Povidone-iodine, with 0.01% Methylrosanilinium Chloride ointment which was applied to the nares once a day for two weeks. A post-bacteriological examination again revealed that MRSA vanished from the nares of six nasal carriers. The minimum inhibitory concentration (MIC) of Methylrosanilinium Chloride was determined by the agar plate dilution method. The 100% MICs of MSSA were 1.0 microgram/ml and of MRSA were 1.0 microgram/ml by Methylrosanilinium Chloride. Moreover we examined the MICs of Methylrosanilinium Chloride against MRSA under the existing 5% Albumin, and consequently the 100% MICs were 4.0 micrograms/ml. Therefore a 0.01% Methylrosanilinium Chloride has sufficient efficacy against MRSA. The reaction of the skin and nasal mucosa to Methylrosanilinium Chloride was examined by using three groups of guinea pigs. 0.1% and 0.01% Methylrosanilinium Chloride ointment and hydrophylic poloid were applied to the nares and skin once a day for two weeks. Post-observation with an opticmicroscope revealed no significant findings. Methylrosanilinium Chloride shows good anti-Staphylococcus aureus ability. Further investigation is needed to determine if Methylrosanilinium Chloride has additional clinical application.

Animals↗
PubMed1994

Presence of chloride-formate exchange in vascular smooth muscle and cardiac cells.

The presence of chloride-formate anion exchange in vascular smooth muscle cells (VSMCs) and cardiac myocytes was investigated. Imposing an outward chloride gradient in sarcolemmal microsomes isolated from canine aorta stimulated [14C]formate uptake compared with the absence of a chloride gradient (24.3 +/- 2.33 versus 9.8 +/- 1.41 pmol/mg protein for 30 seconds, P < .03) and induced transient uphill [14C]formate uptake. The chloride-formate exchange was significantly inhibited in the presence of 1 mmol/L 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid (DIDS) or furosemide (57% and 61%, respectively). Incubation of rat cultured VSMCs in a medium containing [14C]formate resulted in uptake of formate that was significantly DIDS and furosemide sensitive (79.34 +/- 2.47, 43.03 +/- 2.37, and 44.65 +/- 1.68 pmol/mg protein for 4 minutes in control, DIDS, and furosemide groups, respectively). Preincubation of the VSMCs in chloride-free medium significantly reduced the DIDS-sensitive (36.31 versus 16.85 pmol/mg protein for 4 minutes, P < .001) and furosemide-sensitive (34.72 versus 8.78 pmol/mg protein for 4 minutes, P < .001) [14C]formate uptake. These results are compatible with the presence of chloride-formate exchange in VSMCs. Influx of [14C]formate into sarcolemmal vesicles isolated from canine heart was significantly higher in the presence of an outward chloride gradient than in its absence (18.1 +/- 2.3 versus 9.6 +/- 1.7 pmol/mg protein for 30 seconds, P < .03). The chloride-formate exchange was significantly inhibited in the presence of 1 mmol/L DIDS or furosemide (41% and 52%, respectively). We conclude that the distribution of chloride-formate exchange may be more universal than previously suggested.(ABSTRACT TRUNCATED AT 250 WORDS)

4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid↗
PubMed2000

NTP Toxicity Studies of Benzyltrimethylammonium Chloride (CAS No. 56-93-9) Administered by Gavage to F344/N Rats, Sprague-Dawley Rats, and B6C3F1 Mice.

Benzyltrimethylammonium chloride is widely used as a solvent for cellulose, a gelling inhibitor in polyester resins, a chemical intermediate, a paint dispersant, and an acrylic dyeing agent. It is also used in plant growth regulator compositions and synthetic processes. The National Institute of Environmental Health Sciences nominated benzyltrimethylammonium chloride for study due to its high production volume and the potential for occupational exposure, as well as the limited information on toxicity of this chemical. Male and female F344/N rats and B6C3F1 mice received benzyltrimethylammonium chloride by gavage for 16 days or 13 weeks. Animals were evaluated for hematology, clinical chemistry, histopathology, neurotoxicity, and reproductive toxicity. Genetic toxicology studies were conducted in Salmonella typhimurium and in mouse peripheral blood erythrocytes. In the 16-day studies, groups of five male and five female rats received 0, 16, 32, 63, 125, or 250 mg benzyltrimethylammonium chloride/kg body weight in deionized water by gavage, 5 days per week for 16 days. Groups of five male and five female mice received 0, 63, 125, 250, 500, or 1,000 mg/kg benzyltrimethylammonium chloride in deionized water by gavage, 5 days per week for 16 days. All rats in the 125 and 250 mg/kg groups, all mice in the 250, 500, and 1,000 mg/kg groups, and one 125 mg/kg female mouse died on day 1 of the studies. Clinical findings observed in 125 mg/kg male and female rats included abnormal breathing, ataxia, lethargy (males only), nasal and eye discharge, and tremors. Salivation was slightly increased in male and female rats in the 63 mg/kg groups. Female mice in the 125 mg/kg group had a significantly greater absolute liver weight than that of the vehicle controls. No gross or microscopic changes observed in rats or mice were considered related to chemical administration. In the 13-week studies, groups of 10 male and 10 female rats and mice received benzyltrimethylammonium chloride in deionized water by gavage at doses of 0, 12.5, 25, 50, or 100 mg/kg, 5 days per week for 13 weeks. Benzyltrimethylammonium chloride generally had little effect on the body weights of rats or mice. Final mean body weights of dosed animals were within 8% (rats) or 3% (mice) of the control group body weights. The deaths of two female rats and one male and one female mouse administered 100 mg/kg were the result of pharmacologic effects on the cardiovascular system. Some cholinergic effects including chromodacryorrhea, lacrimation, salivation, pupillary constriction, altered gait, and mild tremors were observed at nonlethal doses in rats; these effects were accompanied by alterations in body position. No significant target organ toxicity was observed in dosed rats or mice. Benzyltrimethylammonium chloride was not mutagenic in S. typhimurium strain TA97, TA98, TA100, or TA1535, with or without S9 metabolic activation enzymes. However, significant increases in the frequency of micronucleated normochromatic erythrocytes were found in the peripheral blood of male and female mice administered benzyltrimethylammonium chloride by gavage for 13 weeks. Based on the mortality observed in the 16-day and 13-week studies, rats and mice appeared to be equally sensitive to benzyltrimethylammonium chloride. The minimally toxic dose for rats and mice was estimated to be 50 mg/kg.

Journal Article↗
PubMed2003

Effects of tributyltin chloride on the reproductive system in pubertal male rats.

Detrimental effects of tributyltin (TBT) chloride on the reproductive system were investigated in pubertal male rats. Sixty Sprague-Dawley rats aged with 35 days were assigned to six different groups; negative control receiving vehicle, positive control receiving methyltestosterone (10 mg/kg B.W.), TBT chloride (5 mg/kg B.W., 10 mg/kg B.W., and 20 mg/kg B.W.), and a combination of TBT chloride (10 mg/kg B.W.) and flutamide (10 mg/kg B.W). The animals were treated with test compounds by oral gavage daily for 10 days and sacrificed on the next day of the final treatment. The treatment with TBT chloride at the doses of 10 and 20 mg/kg B.W. significantly decreased seminal vesicle weights, compared to the negative control. The combined treatment of TBT chloride and flutamide caused a significant decrease in accessory sex organ weights, compared to the control and TBT chloride treatments. The treatment with TBT chloride or in the combination with flutamide increased detached debris and sloughed cells in the tubules of epididymis and narrowed seminal vesicles. In addition, the combined treatment with TBT chloride and flutamide caused a noticeable increase in serum androgen level, compared to the negative control. These results suggest that TBT chloride exposed during pubertal period cause partial reproductive disorders in male rats.

Animals↗
PubMed1982

[Comparison of 201T1-chloride and 67Ga-citrate in thyroid tumor scintigraphy].

Twenty-five patients with thyroid tumors were examined by 201T1-chloride and 67Ga-citrate scintigraphy heterochronously in our department. All cases showed the cold nodule with 131I or 99mTc-pertechnetate thyroid scintigraphy and each one was given a histological diagnosis after surgery or excisional biopsy. In 15 cases of thyroid carcinoma, 12 (80%) were positive by 201T1-chloride; 4 (26.7%) were positive by 67Ga-citrate. In examining each histological type, 8 of 9 cases of papillary carcinoma (88.9%) were positive by 201T1-chloride. In 1 negative case the tumor was almost completely encysted; however, they were all negative by 67Ga-citrate. In 2 patients with follicular carcinoma, both of them revealed a positive figure by 201T1-chloride, and one of these with oxyphilic cell carcinoma showed a positive figure by 67Ga-citrate. In 1 case of medullary carcinoma there was slight accumulation with 201T1-chloride, but there was no accumulation with 67Ga-citrate. In 3 cases of undifferentiated carcinoma, 2 patients with small carcinoma showed a negative figure by 201T1-chloride. However, they all showed a positive figure using 67Ga-citrate and this medium also disclosed distant metastases of undifferentiated carcinoma. In 10 patients with thyroid adenoma, 3 (30%) showed a positive figure by 201T1-chloride. Histologically, these were all tubular adenoma, but in all cases of thyroid adenoma 67Ga-citrate revealed a negative figure. From the above mentioned results, the following conclusion were reached. Tumors showing a positive figure by 201T1-chloride that elicited negative results using 67Ga-citrate proved to be differentiated carcinoma or low differentiated types of adenoma. Surgery is indicated in these cases. All of the tumors revealing a positive figure by 67Ga-citrate were highly malignant types. If these tumors showed a negative figure when 201T1-chloride was used, undifferentiated carcinoma was suggested. In undifferentiated carcinoma, 67Ga-citrate scintigraphy is a useful procedure in locating distant metastases, in determining the area to be irradiated, and in judging the effect of therapy.

Adenocarcinoma↗
PubMed1994

Onset of action of mivacurium chloride. A comparison of neuromuscular blockade monitoring at the adductor pollicis and the orbicularis oculi.

BACKGROUND: The optimal site for monitoring neuromuscular blockade for intubations facilitated with mivacurium chloride has not been established. The primary purpose of this evaluation was to determine the difference in onset of neuromuscular blockade between the orbicularis oculi and adductor pollicis in patients administered mivacurium chloride. We also evaluated intubating conditions when intubation was timed to maximal neuromuscular blockade at either the orbicularis oculi or the adductor pollicis. The results for patients administered mivacurium chloride were compared with those for a control group administered succinylcholine. METHODS: In a double-blind randomized design, the time to loss of the compound muscle action potential at the orbicularis oculi and adductor pollicis was monitored in 20 patients administered mivacurium chloride and ten patients administered succinylcholine. After administration of mivacurium chloride (0.15 mg.kg-1), ten patients underwent tracheal intubation at maximal depression of the orbicularis oculi (group 2) and ten patients at maximal depression of the adductor pollicis (group 3). In an additional ten patients the trachea was intubated 60 s after administration of succinylcholine (1 mg.kg-1) (group 1, control). Intubation and evaluation of conditions was performed by one investigator blinded to patient treatments. RESULTS: Loss of compound muscle action potential at the orbicularis oculi and adductor pollicis was more rapid in group 1, and intubation was completed at 86 +/- 26 s. In the patients administered mivacurium chloride, the orbicularis oculi compound muscle action potential was lost 3 min earlier than the adductor pollicis compound muscle action potential. Subsequently, intubation was completed at 134 +/- 50 s in the orbicularis oculi group, whereas the time to intubation was 321 +/- 57 s in the adductor pollicis group. There was no significant differences in intubation conditions between the mivacurium chloride groups. CONCLUSIONS: When monitoring 95% twitch height depression of the orbicularis oculi muscle, intubation can be accomplished in approximately 2 min after administration of mivacurium chloride (0.15 mg.kg-1). Because intubating conditions were comparable to the patients administered succinylcholine or intubated during monitoring of the twitch height depression of the adductor pollicis, we believe that optimal site for monitoring during intubation using mivacurium chloride is the orbicularis oculi muscle.

Action Potentials↗
PubMed1994

Chloride currents in freshly isolated rat retinal pigment epithelial cells.

Cells of the retinal pigment epithelium (RPE) were isolated from neonatal rats. The perforated-patch clamp technique, using amphotericin-B, revealed a chloride current, which was detected as a 4,4'-diisothiocyanostilbene-2,2'-disulfonate (DIDS)-sensitive component. A variety of chloride-channel inhibitors, other than DIDS, also blocked the chloride current, including 9-anthracenecarboxylic acid (9-AC), niflumic acid, 5-nitro-2-(3-phenylpropylamino)-benzoic acid (NPPB) and N-phenylanthranilic acid (DPC). DIDS at 1 mmol l-1 and DPC at 2 mmol l-1 were both more potent than niflumic acid at 200 mumol l-1. The hyperosmotic condition (+50 mosmol) did not affect the chloride current. The hypo-osmotic condition (-80 mosmol), however, led to an increase of total membrane conductance, during which a chloride conductance increase occurred. The membrane-conductance increase, evoked by the hyposmotic condition, ran up and then ran down by itself. As with the steady-state chloride conductance, 1 mmol l-1 DIDS and 2 mmol l-1 DPC were more potent blockers than 200 mumol l-1 niflumic acid. DIDS at 1 mmol l-1 was more effective in blocking the outward component than 2 mmol l-1 DPC, while the inward component was blocked oppositely. When the intracellular calcium concentration was presumed to have increased, using the calcium ionophore, ionomycin, membrane conductance abruptly increased, quickly ran up and then ran down by itself. This included an elevation of a DIDS-sensitive current, and was largely carried by chloride. Chloride currents of rat RPE cells did not appear to be regulated by cyclic AMP.

1-Methyl-3-isobutylxanthine↗
PubMed2000

The role of voltage-gated chloride channels in type II pyrethroid insecticide poisoning.

Pyrethroids act on mammalian sodium channels, but we have previously shown that low concentrations of the type II pyrethroid deltamethrin also decrease the open channel probability (P(o)) of voltage-gated chloride channels. This effect would be expected to amplify the sodium channel-mediated signs of poisoning produced by pyrethroids. In the present study we evaluated potential chloride channel agonists in vitro, and then tested the most effective of these on pyrethroid-poisoned rats to determine the practical significance of chloride channel effects in vivo. Patch clamp experiments showed that, for voltage-gated maxi chloride channels in excised, inside-out patches from mouse N1E 115 neuroblastoma cells, ivermectin (10(-7) M) and pentobarbitone (10(-6) M) significantly increased open channel probability (p </= 0.01 and p </= 0.02, respectively), whereas phenobarbitone, hexobarbitone, mephobarbitone, thiopentone, and barbituric acid did not. This suggested that, if chloride channels were important in vivo, ivermectin and pentobarbitone should antagonize type II pyrethroid poisoning and phenobarbitone should not. Male F344 rats were then pretreated with ivermectin (4 mg/kg iv), equisedative doses of either pentobarbitone (15 mg/kg ip) or phenobarbitone (45 mg/kg ip), or solvent controls. This was followed by deltamethrin (1.5 or 2 mg/kg iv) or the type I pyrethroid cismethrin (4 mg/kg iv). Ivermectin produced a marked fall in deltamethrin-induced salivation (p </= 0.05) and also (in anesthetized rats) in repetitive electromyogram discharge and muscle twitch (p </= 0.01 and p </= 0.05, respectively). Pentobarbitone significantly reduced the motor signs score due to deltamethrin (p </= 0.01). Ivermectin therefore protected against the peripheral signs of deltamethrin poisoning and pentobarbitone protected against the central signs. As expected phenobarbitone had no protective effects. The motor signs produced by the type I pyrethroid cismethrin (which does not act on chloride channels) were not diminished by either barbiturate. The peripheral benzodiazepine receptor blocker PK11195 did not diminish the protective action of ivermectin on the muscle twitch (p </= 0.05), although it partially reversed the block of salivation (p </= 0.05). These results support the hypothesis that the voltage-dependent chloride channel is a toxicologically significant additional site of action for deltamethrin and that the use of chloride channel agonists can provide a rationale for a novel and effective therapy against type II pyrethroid poisoning.

Animals↗
PubMed1994

Vacuolar chloride regulation of an anion-selective tonoplast channel.

Fluctuations in intravacuolar chloride concentrations affected the tonoplast inward (anion flux into the vacuole) currents of sugar beet (Beta vulgaris). Rising vacuolar chloride concentrations induced increases in the levels of nitrate, acetate and phosphate inward currents. These currents, evoked at physiological vacuolar potentials, showed a linear relationship with the concentration of vacuolar chloride between 6 and 100 mM. Single channel currents revealed that rises in vacuolar chloride increased the frequency and probability of channel openings at a given tonoplast potential by reducing the mean closed time of the anion channel. In addition, there was an increase in the gating charge for the channel and a decrease in the free-energy favoring the transition of the channel from the closed to the open state. Vacuolar chloride had a very different effect on malate currents. Increasing chloride concentrations resulted in decreased frequency and open probability of the channel openings, a decrease in the gating charge and an increase in the mean closed time of the channel. Our results support the role for vacuolar chloride concentrations regulating the influx of anions into the vacuole, in addition to osmoregulation. The activation of channel activity by chloride will provide a pathway for the storage of nutrients, such as nitrate and phosphate into the vacuole, while the reduction of the malate currents will allow the use of malate for mitochondrial oxidation and cytoplasmic pH control.

Cell Membrane↗
PubMed2005

Chloride efflux in unstimulated Leydig cells causes autonomous cAMP production and stimulatory/inhibitory steroidogenesis with an efflux inhibitor.

Gonadotropins cause immediate chloride secretion in Leydig cells, which still have an unknown physiological. Thyroid and Leydig cells produce more cAMP and steroids, respectively, under low or chloride-free conditions. Here, we show that chloride efflux mediated by incubation of Mouse Leydig Tumor cells (MLTC-1) in hypotonic or chloride-free isotonic buffers results in more cAMP production without any gonadotropic stimulation. MLTC-1 cells incubated with 0.5mM diphenylamine-2-carboxylate (DPC), a chloride efflux inhibitor, produced increased amounts of testosterone as chloride ions were substituted by gluconate or sulphate ions under isotonic conditions. There was also an up-regulation of steroidogenic acute regulatory protein and 3beta-hydroxysteroid dehydrogenase/isomerase type I mRNAs, without human chorionic gonadotropin. With the exception of cAMP production, 2mM DPC inhibited all of the above, including the transcription of constitutively expressed cholesterol side-chain cleavage enzyme and the L19 house-keeping gene. Although it was speculated that gonadotropin mediated chloride secretion could aid steroid hormone release, we conclude that the real reason for chloride secretion in Leydig cells may be to "kick start" cAMP production.

Animals↗
PubMed1999

Influence of chloride ions on alpha1-adrenoceptor mediated contraction and Ca2+ influx in rat caudal artery.

The objective of the present investigation was to compare and contrast the effects of 8-bromoguanosine 3':5'-cyclic monophosphate (8-Bromo-cyclic GMP), an analogue of guanosine 3':5'-cyclic monophosphate, felodipine, a dihydropyridine Ca2+ channel antagonist, and 5-nitro-2-(3-phenylpropylamino) benzoic acid (NPPB), a putative chloride channel antagonist on alpha1-adrenoceptor mediated contraction and Ca2+ influx in rat caudal artery, in normal physiological salt solution and in chloride-free solution. Isometric contractions and 45Ca2+ influx were measured in isolated rat caudal arterial rings. Phenylephrine induced concentration-dependent contractions were inhibited by 8-Bromo-cyclic GMP (10 microM), felodipine (10 nM) and NPPB (3.0 microM). Removal of chloride ions also impaired phenylephrine-induced contractions. In chloride-free buffer, phenylephrine-induced contractions were partially inhibited by the presence of 8-Bromo-cGMP or felodipine, while NPPB had no effect. Phenylephrine induced 45Ca2+ influx was inhibited by the presence of 8-Bromo-cyclic GMP, felodipine and NPPB. Moreover, removal of chloride ions also inhibited phenylephrine-induced 45Ca2+ influx. The results of our study demonstrate that in the rat caudal artery the inhibitory effects of 8-Bromo-cyclic GMP, felodipine and NPPB, are mediated through a reduction of Ca2+ influx. In addition, chloride ions, in part, play a role in alpha1-adrenoceptor-mediated Ca2+ influx. However, the influence of removal of chloride ions on phenylephrine stimulated contraction is limited. Moreover, 8-Bromo-cyclic GMP and felodipine, but not NPBB, impair phenylephrine-induced contractions in the absence of chloride ions.

Animals↗
PubMed1990

Effect of magnesium chloride on rabbit bronchial smooth muscle.

STUDY OBJECTIVE: The objective of this study was to determine the extent to which magnesium relaxes bronchial smooth muscle during induced contraction. DESIGN: An in-vitro model using bronchial rings from New Zealand White rabbits stimulated to contract by electrical stimulation, histamine, or bethanechol. INTERVENTIONS: Magnesium chloride 1, 6, 16, 36, and 86 mM was added to each tissue bath and resting tension was measured. Electrical stimulation 100 V/100 ms, histamine 10 mM, or bethanechol 6.25 mM was added to washed tissues to induce contraction. This was followed with magnesium chloride 5, 10, and 50 mM, and the response of bronchial smooth muscle was measured. MEASUREMENTS AND MAIN RESULTS: Magnesium chloride 1, 6, 16, 36, and 86 mM decreased the mean +/- SEM resting tension of bronchial rings by 40 +/- 16, 100 +/- 11, 110 +/- 10, 170 +/- 9, and 275 +/- 22 mg, respectively. Electrical stimulation (4) of 100 V/100 ms increased the mean +/- SEM resting tension by 168 +/- 52 mg. Magnesium chloride 5, 15, and 50 mM added to the tissue bath decreased the response to 100 V/100 ms to 65 +/- 27, 40 +/- 23, and 1 +/- 0 mg, respectively. Histamine 10 mM (4) increased mean +/- SEM resting tension by 490 +/- 121 mg. Magnesium chloride 5, 15, and 50 mM decreased the histamine response by 80 +/- 56, 250 +/- 74, and 475 +/- 131 mg, respectively. Bethanechol 6.25 mM (14) increased the mean +/- SEM resting tension by 495 +/- 74 mg. Magnesium chloride (5, 15, 50 mM) decreased bethanechol-induced tension by 52 +/- 18, 184 +/- 26, and 506 +/- 64 mg, respectively. CONCLUSION: Magnesium chloride produced dose-dependent relaxation of bronchial smooth muscle at rest and when stimulated by histamine, bethanechol, or electrical impulse. Calcium chloride was unable to significantly reverse magnesium-induced relaxation. These data support the hypothesis that magnesium relaxes smooth muscle and dilates bronchial rings.

Animals↗
PubMed1999

Hyperpolarization-activated inward potassium and calcium-sensitive chloride currents in beating pacemaker insect neurosecretory cells (dorsal unpaired median neurons).

Hyperpolarization-activated inward currents were studied in single adult cockroach Periplaneta americana pacemaker neurosecretory cells, identified as dorsal unpaired median neurons using the whole-cell patch-clamp technique. Under current clamp, injection of negative current produced a hyperpolarization of the cell membrane with a sag in the membrane potential toward the resting value. Under voltage clamp, the whole-cell current-voltage relationship exhibited an unexpected biphasic aspect. The global hyperpolarization-activated inward current could be dissociated by means of 4-acetamido-4'-isothiocyanostilbene-2,2'-disulfonic acid and tetraethylammonium chloride sensitivity, ionic selectivity, voltage dependence and activation threshold as inward potassium and calcium-sensitive chloride currents. The inward potassium current was activated around -80 mV. The reversal potential followed the potassium equilibrium potential when the extracellular potassium concentration was raised. This current was not dependent on the external sodium concentration and was sensitive to 10 mM tetraethylammonium chloride or 5 mM barium chloride. The hyperpolarization-activated inward calcium-sensitive chloride current was activated in a range of potential 20 mV more positive than the potassium current. The estimated reversal potential (-71 mV) was very close to the equilibrium potential for chloride ions ( 73 mV). Intracellularly applied 4-acetamido-4'-isothiocyanostilbene-2,2'-disulfonic acid, 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid and external application of 1 mM zinc chloride, calcium-free saline or high concentrations of intracellular 1,2-bis-(2-aminophenoxy)ethane-N,N,N',N'-tetra-acetate blocked the inward chloride current. Current-clamp experiments indicated that the inward potassium current accounted for inward rectification of dorsal unpaired median neurons. Our findings report, for the first time in pacemaker neurosecretory cells, the co-existence of two distinct hyperpolarization-activated inward currents which have specialized function in pacemaker activity.

4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid↗
PubMed1979

Effect of potassium chloride on plasma renin activity and plasma aldosterone during sodium restriction in normal man.

The present study was designed to evaluate the spectrum of responses of PRA and plasma aldosterone (PAldo) to a range of oral potassium intakes (0 to 300 mEq of potassium chloride per day) in 20 normal human subjects receiving an electrolyte-free diet. Potassium exhibited a dose-dependent natriuretic effect. The results of the PRA studies indicate that normal dietary amounts (50 mEq/day) of potassium chloride do not prevent the increase in PRA with absolute sodium deprivation and that PRA is maximally stimulated on 150 mEq of potassium chloride per day. The rise in PRA is directly correlated with serum potassium concentration. The results of the PAldo studies indicate that potassium chloride deprivation attenuates PAldo increases due to sodium deprivation and that PAldo is maximally stimulated on 150mEq of potassium chloride per day. The rise in PAldo is directly correlated with serum potassium concentration and with PRA. The administration of 300 mEq/day of potassium chloride caused significant hyperkalemia and blunted both PRA and PAldo increases. Our results suggest that potassium chloride has an important role in the regulation of PRA and PAldo, and that only following potassium chloride deprivation is the PRA/PAldo response dissociated.

Aldosterone↗
PubMed1996

Chloride cells and osmoregulation.

The chloride cells of the gill secretory epithelium of fish that make the transition from fresh water to sea water adapt to the increased salinity by responding to a rapid signal that stimulates chloride secretion. In this paper, data are presented supporting the view that the transient increase in plasma osmolarity that can be measured during the transition is responsible for the stimulation of chloride secretion. A maximal increase of 65 mOsm in the plasma of Fundulus heteroclitus (the killifish) was found during acclimation to sea water. Similar or greater increases of osmolarity induced by mannitol on the basolateral side of isolated opercular epithelial membranes of the same species of fish containing great numbers of chloride cells produced stimulation of chloride secretion detected as the short circuit current. The shrinkage of the chloride cell activates the Na-K-2Cl cotransporter, and the Na/H exchanger and requires the integrity of apical chloride channels and normal levels of Ca. A Cl/HCO3 exchanger did not participate in this osmotic response to higher salinity. Chloride cell volume responses to osmolarity were studied with imagine and quantitative optics.

Adaptation, Physiological↗
PubMed1996

Cytoprotection of kidney epithelial cells by compounds that target amino acid gated chloride channels.

Glycine, strychnine and certain chloride channel blockers were reported to protect cells against lethal cell injury. These effects have been attributed to interactions with membrane proteins related to CNS glycine gated chloride channel receptors. We have investigated the pharmacology of these actions. Madin-Darby canine kidney (MDCK) epithelial cells were depleted of adenosine triphosphate (ATP) by incubation in glucose free medium containing a mitochondrial uncoupler. Medium Ca2+ was adjusted to 100 nM in the presence of an ionophore such that intracellular Ca2+ did not increase, and Ca(2+)-related injury mechanisms were inhibited. This permitted more sensitive quantitation of protection against cell injury attributable to glycine or other agents whose actions might be related to those of the amino acid. Two classes of compounds showed cytoprotective activity in this system: (1) ligands at chloride channel receptors, such as glycine, strychnine and avermectin B1a; (2) chloride channel blockers, including cyanotriphenylboron and niflumic acid, both of which are known to bind to channel domains of CNS glycine receptors. Morphological and functional studies showed that the compounds preserved plasma membrane integrity, but permitted cell swelling. Substitution of medium chloride by gluconate, or chloride salts by sucrose, did not substantially modify lethal damage or its prevention by glycine or other drugs. The compounds did not modify ATP declines. At least for some compounds, cytoprotection appeared to be specific to structural features on the molecules. These observations are consistent with the hypothesis that a plasma membrane protein related to glycine-gated chloride channel receptors plays a significant role in cell injury, but indicate that the mechanisms of injury and protection by compounds active in this system are not related to chloride fluxes.

Adenosine Triphosphate↗
PubMed2000

Potassium-magnesium citrate versus potassium chloride in thiazide-induced hypokalemia.

BACKGROUND: The purpose of this study was to compare the value of potassium-magnesium citrate (KMgCit) with potassium chloride in overcoming thiazide-induced hypokalemia. METHODS: Sixty normal subjects first took hydrochlorothiazide (HCTZ; 50 mg/day). After three weeks of treatment (or earlier if hypokalemia developed), they were randomized to take KMgCit (42 mEq K, 21 mEq Mg, and 63 mEq citrate/day) or potassium chloride (42 mEq/day) for three weeks while continuing on HCTZ. RESULTS: KMgCit significantly increased the serum potassium concentration from 3.42 +/- 0.30 mEq/L on HCTZ alone to about 3.8 mEq/L (P < 0.001). Potassium chloride produced a similar increase in serum potassium concentration from 3.45 +/- 0.44 mEq/L to about 3.8 mEq/L (P < 0. 001). KMgCit significantly increased the serum magnesium concentration by 0.11 to 0.12 mEq/L (P < 0.01), whereas potassium chloride produced a marginal decline or no significant change. KMgCit was less effective than potassium chloride in correcting HCTZ-induced hypochloridemia and hyperbicarbonatemia. KMgCit, but not potassium chloride, significantly increased urinary pH (by about 0.6 unit), citrate (by about 260 mg/day), and urinary magnesium. CONCLUSIONS: KMgCit is equally effective as potassium chloride in correcting thiazide-induced hypokalemia. In addition, KMgCit, but not potassium chloride, produces a small but significant increase in serum magnesium concentration by delivering a magnesium load, and it confers alkalinizing and citraturic actions.

Adult↗
PubMed2000

Isolation and characterization of a Ca(2+)-activated chloride channel from human corneal epithelium.

PURPOSE: Transparency of the cornea is maintained through the activity of secretory mechanisms in the epithelium and endothelium, which offset the tendency of the stroma to imbibe fluid and swell. These secretory mechanisms establish osmotic gradients thereby providing the osmotic driving forces for coupled fluid transport from the stroma into both the tears and the anterior chamber. To further characterize the mechanism of epithelial Cl secretion, we cloned a cDNA encoding a Ca(2+)-dependent chloride channel, an abundant mRNA in human corneal epithelium. We investigated the abundance of all known human chloride channels in corneal epithelium to identify those responsible for regulating chloride conductance in this tissue. METHODS: For the isolation of a full-length cDNA clone, a probe was selected from a set of expressed sequenced tag (EST) clones classified as unique to corneal epithelium (http://bodymap. ims.u-tokyo.ac.jp). The expression patterns of the corresponding gene encoding novel chloride channel gene in human cornea and other tissues were examined by reverse transcription-polymerase chain reaction (RT-PCR). Quantitative PCR was performed to clarify the expression level of the novel chloride channel gene in cornea relative to that in other human tissues. RESULTS: We cloned a new Ca(2+)-activated chloride channel, CLCA2, from corneal epithelium. The full length cDNA clone encoded 943 amino acids with 62% identity to bovine Ca(2+)-activated chloride channel. The CLCA2 gene mapped to human chromosome 1p32. Quantitative expression analysis by RT-PCR showed that it is the most abundant chloride channel in corneal epithelium. CONCLUSION: High and tissue specific expression of the CLCA2 gene in human corneal epithelium implies an important role in corneal transparency maintenance.

Amino Acid Sequence↗