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 u sing the impermeant sulfhydryl complexing agent p-chloromercuriphenyl sulfonate (pCMPS). Methods. Membrane permeability changes were studied by measuring lens voltage and resistance. Ion movements were monitore d by measuring Na-22+ and Ca-45(2+) fluxes, and internal free calcium was monitored by ion-selective microelectrodes. Opacification was quan tified by photographing and analyzing back-scattered light. Results. p CMPS, at concentrations above 1 muM, produced a depolarization of memb rane potential and decrease in membrane resistance. These changes were accompanied by a marked stimulation in Na-22+ and Ca-45(2+) influxes into the lens. There was a concomitant loss of lens transparency, main ly in the bow region. The pCMPS-induced electrical changes could be pr evented by substituting N-methyl-D-glucamine for Na+ in the external m edium. Na+-free solution alone increased Ca-45(2+) influx, and the add ition of pCMPS further stimulated the influx. Quinine (300 muM) was fo und to reduce the pCMPS-induced stimulation of Na-22+ and Ca-45(2+) in fluxes and also to reduce opacification. Conclusions. pCMPS at low con centrations induces many of the cation permeability changes previously found to occur with age and cataract in the lens. The fact that quini ne can ameliorate pCMPS-induced changes in ion movements and opacifica tion suggests a novel approach for membrane-based anticataract strateg ies.