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P. J. Donaldson, K. F. Webb; Cation Channels and Cataract: Two Distinct Non-Selective Cation Channels in Lens Fibre Cells. Invest. Ophthalmol. Vis. Sci. 2008;49(13):1527. doi: https://doi.org/.
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The initiation of lens cataract is associated with depolarization of the lens, and the elevation of intracellular concentrations of Na+ and Ca2+, events consistent with the activation of a non-selective cation (NSC) conductance. Here we report on the identification of two distinct NSC channels in lens fiber cells.
The membrane properties of isolated lens fiber cells were analysed by whole cell patch clamping and ion substitution experiments1.
Isolation of fiber cells from the electrogenic epithelium activated a NSC channel that was strongly inhibited by the broad spectrum NSC channel inhibitor Gd3+, but was only partially blocked by an alternative NSC inhibitor, La3+. In the presence of Gd3+, the membrane currents of isolated fiber cells were dominated by an outwardly rectifying Cl- conductance. Replacement of extracellular Cl- with the impermeant anion gluconate initially inhibited this conductance. In addition, gluconate evoked an isosmotic cell shrinkage, that in turn activated a linear leak conductance that was insensitive to Gd3+, but was inhibited by La3+. Subsequent, replacement of extracellular Na+, with the impermeant cation NMDG, reduced the outward component of this current and confirmed that the shrinkage activated conductance is mediated by a NSC channel.
Our results indicated that the lens contains at least two distinct NSC conductances. A Gd3+-sensitive NSC conductance that is activated by cell swelling and a Gd3+-insensitive, La3+-sensitive conductance that is activated by cell shrinkage. The reciprocal activation of these conductance by changes in cell volume indicates that they may play a role in the modulation of steady state lens volume. Furthermore, the inherent Ca2+-permeability of NSC conductances suggests that their sustained activation may be an early event in the initiation of lens cataract.1. Webb KF, Merriman-Smith BR, Stobie JK, Kistler J & Donaldson PJ. (2004). Invest Ophthalmol Vis Sci 45, 4400-4408.
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