Abstract
Abstract: :
Purpose: Cells of the avascular lens require finely tuned ionic transport mechanisms to maintain ionic and hydration homeostasis and preserve lens clarity. Drug-induced changes in ion channels, transporters or pumps may lead to lens swelling, opacity and eventually cataract (Jacob, T.J., ’99). The purpose of this work is to determine whether cells of the human lens epithelial cell line SRA-01/04 (Ibaraki, et al., 1998) express ion channels that contribute to regulatory cell volume control, and to determine if changes in the conductance of these channels may be markers of cataractogenesis. Methods: Whole cell patch-clamp electrophysiological techniques (conventional and perforated) were used to measure transmembrane currents in isolated SRA 01/04 cells (passage #91-105). Currents were characterized using various channel blockers (e.g. TEA, NPPB, etc.) and pCLAMP stimulation protocols. The effects of osmolarity on channel currents and cell size were also determined. Results: The predominant macroscopic current in the SRA 01/04 cells is an outwardly rectified, TEA-sensitive current that is modulated by changes in extracellular osmolarity. Upon exposure to a hypotonic extracellular environment, SRA-01/04 cells initially swell, outward current increases, and then the cell slowly returns toward its pre-exposure size. Conclusions: TEA-sensitive channels may be involved in the regulatory volume decrease observed in the SRA-01/04 human lens epithelial cells. Drug-induced changes in the conductance of these channels may have implications for ocular toxicity, including lens cataract. Table of Contents
Keywords: cataract • electrophysiology: non-clinical • ion channels