Functional and molecular characterization of a volume‐sensitive chloride current in rat brain endothelial cells

Weikersthal, S. F. von; Barrand, Margery A.; Hladky, Stephen B.

doi:10.1111/j.1469-7793.1999.075aa.x

Cited by 74 publications

(72 citation statements)

References 32 publications

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“…In agreement with this hypothesis is the fact that ClC-5 is expressed in the intestine, mainly in rat colon and a human colonderived cell line HT-29 (37,48,52). It may be possible that ClC-5 acts on intestinal calcium absorption as well as on kidney calcium reabsorption.…”

Section: The Role Of Clc-5 In Mineral Metabolismsupporting

confidence: 62%

“…In rats, ClC-5 is expressed in other tissues besides the kidney, such as brain, lungs, liver, endothelial cells, and colon (31)(32)(33)36). In addition, the human ClC-5 channel is also expressed in endothelial cells, suggesting that the distribution of ClC-5 may not be restricted to the kidney (37). It is well known that protein endocytosis takes place in liver, endothelial cells, and colon.…”

Section: Clc-5 Chloride Channel and Protein Endocytosismentioning

confidence: 95%

“…The distribution of ClC-5 mRNA along the rat nephron reveals that this chloride channel is more abundant in the S 3 segments of proximal tubules, in the cortical and medullary thick ascending limb of Henles loop, and in cortical collecting ducts (CCD) (33,34,36,37). An independent group using in situ hybridization further confirmed the expression of the ClC-5 channel on these segments (32).…”

Section: The Role Of Clc-5 In Mineral Metabolismmentioning

confidence: 99%

“…The hypothesis that higher levels of urinary calcium lead to precipitation of calcium salts and then to stone formation is well accepted today (1,2,8,9). Although ClC-5 seems to be expressed mainly in the human kidney (the major site of the disease), it is also expressed in rat colon, brain, and lungs (33,34,(36)(37)(38)48,49) and in Xenopus oocytes (50).…”

Section: The Role Of Clc-5 In Mineral Metabolismmentioning

confidence: 99%

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ClC-5 chloride channel and kidney stones: what is the link?

Silva

Morales

Lopes

2001

Braz J Med Biol Res

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Nephrolithiasis is one of the most common diseases in the Western world. The disease manifests itself with intensive pain, sporadic infections, and, sometimes, renal failure. The symptoms are due to the appearance of urinary stones (calculi) which are formed mainly by calcium salts. These calcium salts precipitate in the renal papillae and/ or within the collecting ducts. Inherited forms of nephrolithiasis related to chromosome X (X-linked hypercalciuric nephrolithiasis or XLN) have been recently described. Hypercalciuria, nephrocalcinosis, and male predominance are the major characteristics of these diseases. The gene responsible for the XLN forms of kidney stones was cloned and characterized as a chloride channel called ClC-5. The ClC-5 chloride channel belongs to a superfamily of voltage-gated chloride channels, whose physiological roles are not completely understood. The objective of the present review is to identify recent advances in the molecular pathology of nephrolithiasis, with emphasis on XLN. We also try to establish a link between a chloride channel like ClC-5, hypercalciuria, failure in urine acidification and protein endocytosis, which could explain the symptoms exhibited by XLN patients.

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Section: The Role Of Clc-5 In Mineral Metabolismsupporting

confidence: 62%

Section: Clc-5 Chloride Channel and Protein Endocytosismentioning

confidence: 95%

Section: The Role Of Clc-5 In Mineral Metabolismmentioning

confidence: 99%

Section: The Role Of Clc-5 In Mineral Metabolismmentioning

confidence: 99%

See 2 more Smart Citations

ClC-5 chloride channel and kidney stones: what is the link?

Silva

Morales

Lopes

2001

Braz J Med Biol Res

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“…The large currents at depolarizing potentials may be due to an increase in the local concentration of chloride at the binding site of volume-activated Cl Ϫ channel, which promotes channel opening (19). The relatively slower channel inactivation observed at positive potentials was also observed in rat brain endothelial cells (29) and rabbit nonpigmented ciliary epithelial cells (24). Much faster inactivation at positive potentials has been reported in canine colonic smooth muscle (2) and human prostate cancer cells (25).…”

Section: This Is the First Report On Volume-activated CLmentioning

confidence: 82%

Volume-activated chloride currents in interstitial cells of Cajal

Park

McKay

Zhu

et al. 2005

American Journal of Physiology-Gastrointestinal and Liver Physi

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cells of Cajal (ICC) undergo marked morphological changes on contraction of the musculature, making it essential to understand properties of mechanosensitive ion channels. The whole cell patch-clamp technique was used to identify and to characterize volume-activated Cl Ϫ currents in ICC cultured through the explant technique. Hypotonic solutions (Ϸ210 mosM) activated an outwardly rectifying current, which reversed near the equilibrium potential for Cl Ϫ . Time-dependent inactivation occurred only at pulse potentials of ϩ80 mV, with a time constant of 478 Ϯ 182 ms. The degree of outward rectification was calculated using a rectification index, the ratio between the slope conductances of ϩ65 and Ϫ55 mV, which was 13.9 Ϯ 1.5 at 76 mM initial extracellular Cl Ϫ concentration. The sequence of relative anion permeability of the outwardly rectifying Cl Ϫ channel wasThe chloride channel blockers, DIDS and 5-nitro-2-(3-phenlypropl-amino)benzoic acid, caused a voltage-dependent block of the outwardly rectifying Cl Ϫ current, inhibition occurring primarily at depolarized potentials. On exposure to hypotonic solution, the slope conductance significantly increased at the resting membrane potential (Ϫ70 mV) from 1.2 Ϯ 0.2 to 2.0 Ϯ 0.4 nS and at the slow-wave plateau potential (Ϫ35 mV) from 2.1 Ϯ 0.3 to 5.0 Ϯ 1.0 nS. The current was constitutively active in ICC and contributed to the resting membrane potential and excitability at the slow-wave plateau. In conclusion, swelling or volume change will depolarize ICC through activation of outwardly rectifying chloride channels, thereby increasing cell excitability. gut motility; intestinal peristalsis; distension; pacemaker cells INTERSTITIAL CELLS OF CAJAL (ICC) are c-kit-positive interstitial cells within the gut musculature, connected to smooth muscle cells by gap junctions and to enteric nerve varicosities by special synapselike junctions (27). These features are common to most ICC subtypes in most species despite the fact that the dominant function of the ICC subtypes might differ. A single ICC may be connected to 10 or more smooth muscle cells (21). Hence, muscle cell contraction and relaxation will affect ICC. Indeed, in a recent study, dramatic structural changes were shown to occur in ICC in the mouse small intestine on distension (28). Before these studies, based primarily on structural information, it was already hypothesized that ICC might be stretch receptors conveying information about contractility and stretch of the musculature to smooth muscle cells and enteric nerves (4,22). To understand the physiological basis of ICC responding to the changing contractile state of the gut musculature, it is necessary to understand the characteristics and eventually the role of volume-activated ion channels in ICC. Therefore, the objective of the present study was to identify and characterize ion channels that were responsive to volume changes (cell swelling). In the present experiments, we used a patch-clamp technique to test this hypothesis and found that ICC generate volume-ac...

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