Walsh S P, Patterson J W
Department of Physiology, University of Connecticut Health Center, Farmington 06032.
Exp Eye Res. 1994 Mar;58(3):257-65. doi: 10.1006/exer.1994.1016.
Hydrogen peroxide, in concentrations of 10-1000 microM, produces two major changes in the current-voltage relationships associated with the equatorial potassium current of the lens. First, the resting and reversal potentials become more negative than they were prior to treatment with hydrogen peroxide and second, the membrane resistance related to the equatorial current is decreased. The shift in the resting and reversal potentials is in the opposite direction from that produced by ouabain. Based on the Nernst equation, the shift in the reversal potential suggests that there is an increase in the concentration of potassium in the lens. The 86Rb uptake and efflux are increased. These observations suggest that hydrogen peroxide stimulates the Na,K-pump. The decrease in membrane resistance is inhibited by 100 microM of quinine, a calcium-dependent potassium channel blocker, and does not decrease in a calcium-free medium. This suggests that the decrease in resistance may be secondary to an increase in lenticular calcium. These effects of hydrogen peroxide are similar to those of p-chloromercuriphenylsulfonate (pCMPS), a nearly impermeant sulfhydryl binding agent, and suggest that permeant hydrogen peroxide may increase calcium influx by acting on sulfhydryl groups on the outer surface of lens membranes. Verapamil, a calcium channel blocker, is reported to prevent cataract formation. D600, the methoxy analogue of verapamil, is a calcium channel blocker that increases the resistance associated with the equatorial current in the presence and absence of hydrogen peroxide. The gadolinium ion has a similar effect. Thus, D600 and Gd3+ partially counteract the reduction in membrane resistance produced by 50 microM hydrogen peroxide.
浓度为10 - 1000微摩尔的过氧化氢会使晶状体赤道部钾电流的电流-电压关系发生两个主要变化。首先,静息电位和反转电位比用过氧化氢处理前变得更负,其次,与赤道部电流相关的膜电阻降低。静息电位和反转电位的变化方向与哇巴因引起的变化相反。根据能斯特方程,反转电位的变化表明晶状体中钾浓度增加。86Rb的摄取和流出增加。这些观察结果表明过氧化氢刺激了钠钾泵。膜电阻的降低被100微摩尔的奎宁(一种钙依赖性钾通道阻滞剂)抑制,并且在无钙培养基中不会降低。这表明电阻的降低可能继发于晶状体钙的增加。过氧化氢的这些作用与对氯汞苯磺酸盐(pCMPS,一种几乎不渗透的巯基结合剂)的作用相似,这表明可渗透的过氧化氢可能通过作用于晶状体膜外表面的巯基来增加钙内流。据报道,钙通道阻滞剂维拉帕米可预防白内障形成。维拉帕米的甲氧基类似物D600是一种钙通道阻滞剂,在有和没有过氧化氢的情况下都会增加与赤道部电流相关的电阻。钆离子也有类似作用。因此,D600和Gd3 +部分抵消了50微摩尔过氧化氢引起的膜电阻降低。