Bicarbonate Transporters In Retinal Pigment Epithelium And Functional Coupling To Other Retinal Cell Layers

The subretinal, as well as intracellular, pH of RPE is linked to the transepithelial transport of HCO3-. Directional HCO3- transport is dependent on the apical transmembrane potential and intracellular HCO3- concentration, allowing the HCO3- transport system to regulate the transport direction in response to pH changes. Under higher intracellular and subretinal pH, HCO3- is taken into the RPE cells by the Na+/HCO3- cotransporter in the apical membranes, and leaves the cell through the basolateral membrane in exchange for Cl- in a manner mediated by the Cl-/HCO3- exchanger (subretinal to choroid directed HCO3- transport). At low intracellular and subretinal pH, HCO3- is taken up by the Cl-/HCO3- exchanger at the basolateral membrane and leaves the cell through the Na+/HCO3- cotransporter in the apical membrane (HCO3- transport from the choroid to the subretinal space) (84). In addition, Seg-awa et al. (85) have shown that elevated bicarbonate concentrations, applied basally, depolarized the apical membrane of cat retinal pigment epithelium-choroid tissue and decreased the potential across the RPE. In contrast, similar doses applied apically hyperpolarized the apical membrane of the RPE and resulted in an increase in the potential across RPE, suggesting the importance of bicarbonate fluxes across retinal pigment epithelium (85). Furthermore, increasing the apical extracellular K+ to levels mimicking fluctuations during the light-dark cycle have resulted in alkalinization of RPE, in a response that was attenuated by either DIDS or removal of bicarbonate, which further supports a close relationship between photoreceptor function and changes in intracellular pH in RPE (86).

RPE has an electrogeneic Na+/HCO3- cotransporter that operates by secretion of three Na+ ions and one HCO3- ion (87,88), and NBC1 is specifically expressed in the human choriocapillaris (89). Bok et al. (81) have reported the expression of pNBCl at the apical membranes in rat RPE. Lin et al. (89) have also shown that apical membranes of frog RPE contain a DIDS-sensitive electrogenic Na+/HCO3- cotransporter and suggested that such a mechanism accounts for around 80% of acid removal in frog RPE. Similarly, Kenyon et al. (88) have shown that explants of bovine retinal pigment epithelium-choroid possess DIDS-sensitive electrogenic Na+/HCO3- cotrans-porters at both apical and basal membranes. Both acid and alkali recovery were HCO3-dependent and can be blocked by DIDS applied on either apical or basal membranes. Basal Cl- removal, or addition of basal HCO3-, caused HCO3- and Cl-dependent alkalini-zations, respectively.

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