Altered visual function in monocarboxylate transporter 3 (Slc16a8) knockout mice
Altered visual function in monocarboxylate transporter 3 (Slc16a8) knockout mice
复制标题
DOI：
10.1152/ajpcell.00124.2008
复制
发表时间：
2008-08-01
影响因子：
5.5
通讯作者：
Philp, Nancy J.
中科院分区：
文献类型：
--
作者：
Daniele, Lauren L.;Sauer, Brian;Philp, Nancy J.
为了满足感光细胞的高能量需求，外视网膜通过糖酵解和氧化途径代谢葡萄糖，导致乳酸和二氧化碳的大量产生。 Mct3 是一种质子耦合单羧酸转运蛋白，其位置至关重要，有助于将乳酸和 H+ 转运出视网膜，因此可以在外视网膜的 pH 和离子稳态中发挥作用。 Mct3优先在视网膜色素上皮的基底外侧膜中表达，并与辅助蛋白CD147形成异聚复合物。为了检查 Mct3 在视网膜中的生理作用，我们生成了 Mct3 (slc16A8) 中的靶向缺失小鼠。 4至36周龄Mct3(-/-)小鼠的整体视网膜组织学表现正常。在缺少 Mct3 的情况下，CD147 的表达从基底外侧而非顶端 RPE 中丢失。相对于野生型小鼠，Mct3(-/-) 小鼠的暗视视网膜电图 (ERG) 的饱和 a 波幅度 (a(max)) 减少了大约两倍。视网膜中乳酸含量增加四倍表明视网膜外层 pH 值降低。在来自灌注视网膜切片的单细胞记录中，单杆光电流（J（最大））的饱和幅度相当，表明Mct3（-/-）小鼠感光细胞本质上是健康的。基于这些数据，我们假设 Mct3 的破坏会导致视网膜下腔 pH 值的潜在可逆下降，从而降低光抑制感光电流的强度。
To meet the high-energy demands of photoreceptor cells, the outer retina metabolizes glucose through glycolytic and oxidative pathways, resulting in large-scale production of lactate and CO2. Mct3, a proton-coupled monocarboxylate transporter, is critically positioned to facilitate transport of lactate and H+ out of the retina and could therefore play a role in pH and ion homeostasis of the outer retina. Mct3 is preferentially expressed in the basolateral membrane of the retinal pigment epithelium and forms a heteromeric complex with the accessory protein CD147. To examine the physiological role of Mct3 in the retina, we generated mice with a targeted deletion in Mct3 (slc16A8). The overall retinal histology of 4- to 36-wk-old Mct3(-/-) mice appeared normal. In the absence of Mct3, expression of CD147 was lost from the basolateral but not apical RPE. The saturated a-wave amplitude (a(max)) of the scotopic electroretinogram (ERG) was reduced by approximately twofold in Mct3(-/-) mice relative to wildtype mice. A fourfold increase in lactate in the retina suggested a decrease in outer-retinal pH. In single-cell recordings from superfused retinal slices, saturating amplitudes of single rod photocurrents (J(max)) were comparable indicating that Mct3(-/-) mouse photoreceptor cells were inherently healthy. Based on these data, we hypothesize that disruption of Mct3 leads to a potentially reversible decrease in subretinal space pH, thereby reducing the magnitude of the light suppressible photoreceptor current.