pCMPS-induced changes in lens membrane permeability and transparency.

PURPOSE To investigate the role of externally facing membrane protein sulfhydryl groups in controlling lens permeability and transparency using the impermeant sulfhydryl complexing agent p-chloromercuriphenyl sulfonate (pCMPS). METHODS Membrane permeability changes were studied by measuring lens voltage and resistance. Ion movements were monitored by measuring 22Na+ and 45Ca2+ fluxes, and internal free calcium was monitored by ion-selective microelectrodes. Opacification was quantified by photographing and analyzing back-scattered light. RESULTS pCMPS, at concentrations above 1 microM, produced a depolarization of membrane potential and decrease in membrane resistance. These changes were accompanied by a marked stimulation in 22Na+ and 45Ca2+ influxes into the lens. There was a concomitant loss of lens transparency, mainly in the bow region. The pCMPS-induced electrical changes could be prevented by substituting N-methyl-D-glucamine for Na+ in the external medium. Na(+)-free solution alone increased 45Ca2+ influx, and the addition of pCMPS further stimulated the influx. Quinine (300 microM) was found to reduce the pCMPS-induced stimulation of 22Na+ and 45Ca2+ influxes and also to reduce opacification. CONCLUSIONS pCMPS at low concentrations induces many of the cation permeability changes previously found to occur with age and cataract in the lens. The fact that quinine can ameliorate pCMPS-induced changes in ion movements and opacification suggests a novel approach for membrane-based anticataract strategies.