May 2008
Volume 49, Issue 13
Free
ARVO Annual Meeting Abstract  |   May 2008
Cation Channels and Cataract: Two Distinct Non-Selective Cation Channels in Lens Fibre Cells
Author Affiliations & Notes
  • P. J. Donaldson
    Department of Physiology, University of Auckland, Auckland, New Zealand
  • K. F. Webb
    Department of Physiology, University of Auckland, Auckland, New Zealand
  • Footnotes
    Commercial Relationships  P.J. Donaldson, None; K.F. Webb, None.
  • Footnotes
    Support  Health Research Council of New Zealand, the Marsden Fund and University of Auckland Research Committee.
Investigative Ophthalmology & Visual Science May 2008, Vol.49, 1527. doi:https://doi.org/
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    • Get Citation

      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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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose: : 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.

Methods: : The membrane properties of isolated lens fiber cells were analysed by whole cell patch clamping and ion substitution experiments1.

Results: : 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.

Conclusions: : 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.

Keywords: ion channels • electrophysiology: non-clinical • cataract 
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