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