CO2-induced ion and fluid transport in human retinal pigment epithelium.
CO2-induced ion and fluid transport in human retinal pigment epithelium.
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DOI：
10.1085/jgp.200810169
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发表时间：
2009-06
期刊：
影响因子：
--
通讯作者：
Miller SS
中科院分区：
文献类型：
--
作者：
Adijanto J;Banzon T;Jalickee S;Wang NS;Miller SS
在完整的眼睛中，从浅色到深色的转变改变了分离感光器外段和视网膜色素上皮（RPE）的顶膜的视网膜下间隙（SRS）中的pH， [Ca2+]和[K]。除了这些变化，视网膜的耗氧量增加，同时二氧化碳和水释放到SRS。RPE通过将这些代谢副产物运送到脉络膜血液供应来维持SRS的pH值和体积平衡。在体外，我们通过将顶浴CO2从5%增加到13%来模拟从浅色到深色的转变；使细胞pH从7.37±0.05降至7.14±0.06 （n = 13）。我们对天然和培养的胎人RPE的分析表明，顶膜对二氧化碳的渗透性（≈10倍；n = 7）明显高于底侧膜，这可能是由于其暴露表面积更大。有限的CO2在基底侧膜上的扩散促进了碳酸酐酶介导的HCO3通过基底侧膜Na/nHCO3共转运体运输。该转运体的活性通过提高顶浴CO2而增加，并通过多唑胺而降低。增加顶浴CO2也通过增加顶膜Na摄取使细胞内Na从15.7±3.3 mM增加到24.0±5.3 mM （n = 6; P < 0.05）。co2诱导的酸化还抑制了基底侧膜Cl/HCO3交换，使净稳态流体吸收率从2.8±1.6µl × cm - 2 × hr - 1增加到6.7±2.3µl （n = 5; P < 0.05）。目前的实验表明，RPE如何适应黑暗中增加的二氧化碳和水的视网膜生产，从而防止SRS酸中毒。这一自稳态过程将保持光感受器外段与RPE在黑暗和光照下的密切解剖关系，从而保护光感受器的健康。
In the intact eye, the transition from light to dark alters pH, [Ca2+], and [K] in the subretinal space (SRS) separating the photoreceptor outer segments and the apical membrane of the retinal pigment epithelium (RPE). In addition to these changes, oxygen consumption in the retina increases with a concomitant release of CO2 and H2O into the SRS. The RPE maintains SRS pH and volume homeostasis by transporting these metabolic byproducts to the choroidal blood supply. In vitro, we mimicked the transition from light to dark by increasing apical bath CO2 from 5 to 13%; this maneuver decreased cell pH from 7.37 ± 0.05 to 7.14 ± 0.06 (n = 13). Our analysis of native and cultured fetal human RPE shows that the apical membrane is significantly more permeable (≈10-fold; n = 7) to CO2 than the basolateral membrane, perhaps due to its larger exposed surface area. The limited CO2 diffusion at the basolateral membrane promotes carbonic anhydrase–mediated HCO3 transport by a basolateral membrane Na/nHCO3 cotransporter. The activity of this transporter was increased by elevating apical bath CO2 and was reduced by dorzolamide. Increasing apical bath CO2 also increased intracellular Na from 15.7 ± 3.3 to 24.0 ± 5.3 mM (n = 6; P < 0.05) by increasing apical membrane Na uptake. The CO2-induced acidification also inhibited the basolateral membrane Cl/HCO3 exchanger and increased net steady-state fluid absorption from 2.8 ± 1.6 to 6.7 ± 2.3 µl × cm−2 × hr−1 (n = 5; P < 0.05). The present experiments show how the RPE can accommodate the increased retinal production of CO2 and H2O in the dark, thus preventing acidosis in the SRS. This homeostatic process would preserve the close anatomical relationship between photoreceptor outer segments and RPE in the dark and light, thus protecting the health of the photoreceptors.
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影响因子：
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作者：
FISHMAN, GA;GILBERT, LD;JAMPOL, LM
通讯作者：
JAMPOL, LM
影响因子：
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