Localised Fibre Cell Swelling Characteristic of Diabetic Cataract Can Be Induced in Normal Rat Lens Using the Chloride Channel Blocker 5-Nitro-2-(3-Phenylpropylamino) Benzoic Acid

Tunstall, Mark J.; Eckert, Reiner; Donaldson, Paul J.; Kistler, Joerg

doi:10.1159/000055553

Cited by 32 publications

(12 citation statements)

References 3 publications

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“…Our finding that an anion conductance dominates the membrane properties of longer isolated fiber cells is consistent with earlier experiments that reported modulation of resting lens voltage by extracellular Cl Ϫ removal (1, 3, 15), a series of morphological studies on whole lens organs cultured under isosmotic conditions that were exposed to a variety of anion channel inhibitors (8,40,51,55), and patch-clamp studies that previously detected anion channel activity in isolated fiber cells and excised membrane patches (54,56). In this study, we demonstrate, for the first time, that isolated fiber cells and whole lenses share a common lyotropic anion selectivity sequence (Table 3).…”

Section: Discussionsupporting

confidence: 90%

Differentiation-dependent changes in the membrane properties of fiber cells isolated from the rat lens

Webb

Donaldson²

2008

American Journal of Physiology-Cell Physiology

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Impedance measurements in whole lenses showed that lens fiber cells possess different permeability properties to the epithelial cells from which they differentiate. To confirm these observations at the cellular level, we analyzed the membrane properties of fiber cells isolated in the presence of the nonselective cation channel inhibitor Gd3+. Isolated fiber cells were viable in physiological [Ca2+] and exhibited a range of lengths that reflected their stage of differentiation. Analysis of a large population of fiber cells revealed a subgroup of cells whose conductivity matched values measured in the whole lens (1). In this group of cells, membrane resistance, conductivity, and reversal potential all varied with cell length, suggesting that the process of differentiation is associated with a change in the membrane properties of fiber cells. Using pharmacology and ion substitution experiments, we showed that newly differentiated fiber cells (<150 microm) contained variable combinations of Ba2+-and tetraethylammonium-sensitive K+ currents. Longer fiber cells (150-650 microm) were dominated by a lyotropic anion conductance, which also appears to plays a role in the intact lens. Longer cells also exhibited a low-level, nonselective conductance that was eliminated by the replacement of extracellular Na+ with N-methyl-d-glucamine, indicating that the lens contains both Gd3+-sensitive and -insensitive nonselective cation conductances. Fiber cell differentiation is therefore associated with a shift in membrane permeability from a dominant K+ conductance(s) toward larger contributions from anion and nonselective cation conductances as fiber cells elongate.

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Section: Discussionsupporting

confidence: 90%

Differentiation-dependent changes in the membrane properties of fiber cells isolated from the rat lens

Webb

Donaldson²

2008

American Journal of Physiology-Cell Physiology

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“…Previous studies have suggested that rat lens volume is regulated over the course of 48 h, with maximal swelling occurring at 12-18 h post osmotic challenge (Patterson and Fournier 1976;Tunstall et al 1999). This time point was therefore selected to investigate the eVect of osmotic stress on lens wet weight, transparency, and Wber cell morphology (Fig.…”

Section: Resultsmentioning

confidence: 99%

Differential membrane redistribution of P2X receptor isoforms in response to osmotic and hyperglycemic stress in the rat lens

Suzuki-Kerr

Lim

Vlajkovic

et al. 2009

Histochem Cell Biol

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P2X(1, 2, 3, 4, 6 and 7) are all expressed in a differentiation-dependent manner in the rat lens. However, in the lens outer cortex the subcellular distribution of all P2X isoforms is predominantly associated with a pool of receptors located in cytoplasmic vesicles. Here we investigate whether osmotic and hyperglycemic stress can alter the subcellular distribution of this cytoplasmic pool of P2X receptors. We show that in a discrete zone of the deeper outer cortex an isoform and stimulus-specific shift in the subcellular distribution of P2X receptors occurs from the cytoplasm to defined membrane domains. In response to hypertonic stress P2X(1) and P2X(4) isoforms became more closely associated with the broad sides of fiber cells, while under hypotonic conditions P2X(4) and P2X(6) isoforms associate with the narrow side membranes. No such changes in subcellular distribution were observed for P2X(2,3 and 7) isoforms. Lens cultured in 50 mM glucose exhibited cell swelling in this zone but only P2X(4) associated with narrow side membranes. Our results indicate P2X receptors can be differentially recruited to specific membrane domains of lens fiber cells by osmotic and hyperglycemic stress. Furthermore they suggest the involvement of specific P2X isoforms in the regulation of fiber cell volume and the initiation of diabetic cataract.

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“…2 More recently, the role that Cl Ϫ ions play in this process has been further investigated by culturing rat lenses in the presence of a range of Cl Ϫ channel inhibitors, including 5-nitro-2-(3-phenylpropylamino) benzoic acid (NPPB). [3][4][5] In these experiments, exposure of lenses cultured under both hypotonic and isotonic conditions to Cl Ϫ channel inhibitors produced an increase in lens volume. 3 This indicates that, under normal isotonic conditions, a constitutively active flux of Cl Ϫ ions exists in the lens that regulates fiber cell volume and thereby maintains lens transparency.…”

mentioning

confidence: 99%

“…[3][4][5] In these experiments, exposure of lenses cultured under both hypotonic and isotonic conditions to Cl Ϫ channel inhibitors produced an increase in lens volume. 3 This indicates that, under normal isotonic conditions, a constitutively active flux of Cl Ϫ ions exists in the lens that regulates fiber cell volume and thereby maintains lens transparency.…”

mentioning

confidence: 99%

Roles for KCC Transporters in the Maintenance of Lens Transparency

Chee¹,

Kistler

Donaldson³

2006

Invest. Ophthalmol. Vis. Sci.

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The rat lens expresses three KCC transporter isoforms (KCC1, -3, and -4) in a differentiation-dependent manner. Modulation of transporter activity and subcellular localization suggests that multiple KCC transporters mediate KCl efflux in peripheral fiber cells in a dynamic fashion. These results indicate that, in addition to Cl- channels, KCC transporters play a role in mediating a circulating flux of Cl- ions, which contributes to the maintenance of lens transparency through controlling the steady state volume of lens fiber cells.

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Localised Fibre Cell Swelling Characteristic of Diabetic Cataract Can Be Induced in Normal Rat Lens Using the Chloride Channel Blocker 5-Nitro-2-(3-Phenylpropylamino) Benzoic Acid

Cited by 32 publications

References 3 publications

Differentiation-dependent changes in the membrane properties of fiber cells isolated from the rat lens

Differentiation-dependent changes in the membrane properties of fiber cells isolated from the rat lens

Differential membrane redistribution of P2X receptor isoforms in response to osmotic and hyperglycemic stress in the rat lens

Roles for KCC Transporters in the Maintenance of Lens Transparency

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