Effects of oxidants on lens transport

Hydrogen peroxide is associated with the development of cataracts. As an oxidant, it can act on the sulfhydryl groups of proteins and alter the transport properties of membranes. A nearly impermeant sulfhydryl binding agent is p-chloromercuriphenylsulfonate (p-CMPS). The changes in the current-voltage relationship of the equatorial potassium current produced by hydrogen peroxide and p-CMPS are similar. The authors studied the effects of p-CMPS to determine the possible effects of binding extracellular sulfhydryl groups. With a vibrating probe and microelectrodes, the authors saw three sequential effects of 0.5-5.0 microM p-CMPS. The first phase was a shift of the reversal potential, which is equivalent to the potassium equilibrium potential, to more negative values. The current-voltage relationship (J vs PD) shifted in a manner opposite to that produced by ouabain. The 86Rb uptake was stimulated. Ouabain blocked this initial phase. The second phase was a decrease in the resistance. The effects seen were similar to those described in other tissues after the intracellular injection of small amounts of Ca++. This second phase was inhibited by the removal of Ca++ from the medium and also by the addition of quinine to the medium. The third phase consisted of a depolarization of the lens. This effect has been described by others with larger concentrations of p-CMPS and is accompanied by an influx of Na+ and Ca++. The results suggested that micromolar quantities of extracellular p-CMPS sequentially stimulate the Na, K-pump; activate Ca(++)-dependent K+ channels; and open nonspecific channels. It is suggested that the second phase may play a role in cateractogenesis.