Ion transport mechanisms in human retinal pigment epithelium (RPE)

Quinn, R. H.; Miller, S. Shea

doi:10.1016/0014-4835(92)90318-m

Cited by 74 publications

(124 citation statements)

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“…Previous functional studies of human RPE have identified two functionally distinct chloride channels located in the basolateral membrane, a cAMP-regulated channel and a calciumregulated channel (28). In the present study, whole cell patch-clamp measurements in primary cultures of haRPE cells demonstrated an outwardly rectifying current that was reduced by replacement of chloride in the bathing solution with iodide or gluconate.…”

Section: Discussionsupporting

confidence: 58%

Oxidant and antioxidant modulation of chloride channels expressed in human retinal pigment epithelium

Weng

Godley

Jin

et al. 2002

American Journal of Physiology-Cell Physiology

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little is known about the molecular nature of chloride channels in human adult RPE (haRPE) or the effects of oxidative stress on membrane conductance properties. In the present study, we assessed ClC channel and cystic fibrosis transmembrane conductance regulator (CFTR) expression and membrane chloride conductance properties in haRPE cells. ClC-5, ClC-3, ClC-2, and CFTR mRNA expression was confirmed with RT-PCR analysis, and protein expression was detected with Western blot analysis and immunofluorescence microscopy. Whole cell recordings of primary cultures of haRPE showed an outwardly rectifying chloride current that was inhibited by the oxidant H2O2. The inhibitory effects of H2O2 were reduced in cultured human RPE cells that were incubated with precursors of glutathione synthesis or that were stably transfected to overexpress glutathione S-transferase. These findings indicate a possible role for ClC channels in haRPE cells and suggest possible redox modulation of human RPE chloride conductances.immunocytochemistry; patch clamp; glutathione; glutathione S-transferase RETINAL PIGMENT EPITHELIUM (RPE) comprises part of the blood-retina barrier and functions in several processes that are vital for the preservation of sight. Among the crucial roles of this epithelium is the regulation of the volume and electrolyte composition of the subretinal space. This function is achieved largely by regulated transepithelial transport of chloride from the subretinal space to the choroid with the obligatory movement of water. Disruption of RPE chloride transport can result in the accumulation of fluid in the subretinal space and subsequent retinal detachment (3, 26).Chloride transport across the RPE is mediated in part by chloride channels that are stimulated by calcium and cAMP (Ref. 28; cf. Refs. 13,14). In recent whole cell patch-clamp recordings in SV40-transformed cultured human fetal RPE (hfRPE) cells, we (39) identified an outwardly rectifying chloride current that was stimulated by cAMP but was inhibited by the chloride channel blocker DIDS, acidic bathing solutions, or low concentrations of the oxidative agent H 2 O 2 . The molecular identity of the chloride channel(s) responsible for this current was not determined. However, these cells expressed several candidate chloride channels including cystic fibrosis transmembrane conductance receptor (CFTR) and members of the ClC chloride channel family Ref. 39). At present, little is known about the expression of ClC chloride channels in the intact human RPE.Recent evidence suggests that the ClC family of voltage-gated chloride channels may be crucial for retinal function. At least three members of this family are associated with retinal degenerations in mice. Specifically, transgenic mice that were deficient for ClC-3 (34), ClC-2 (6), or ClC-7 (17) were found to develop retinal degenerations and blindness within weeks after birth. The basis of these degenerations is not presently understood.The finding of ClC channel expression in human fetal cells and the consequences of ...

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Section: Discussionsupporting

confidence: 58%

Oxidant and antioxidant modulation of chloride channels expressed in human retinal pigment epithelium

Weng

Godley

Jin

et al. 2002

American Journal of Physiology-Cell Physiology

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“…Cell Type-Specific Variations in Sorting The Na,K-ATPase localizes to the apical membranes of cells of the retinal pigment epithelium (RPE) [113][114][115][116] and the choroid plexus. [117][118][119][120] Although these cells exhibit an apical distribution of this canonical basolateral protein, other proteins that serve as standard apical and basolateral markers retain their characteristic distributions.…”

Section: Cell-specific Variations In Traffickingmentioning

confidence: 99%

Trafficking to the Apical and Basolateral Membranes in Polarized Epithelial Cells

Stoops

Caplan

2014

Journal of the American Society of Nephrology

100

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Renal epithelial cells must maintain distinct protein compositions in their apical and basolateral membranes in order to perform their transport functions. The creation of these polarized protein distributions depends on sorting signals that designate the trafficking route and site of ultimate functional residence for each protein. Segregation of newly synthesized apical and basolateral proteins into distinct carrier vesicles can occur at the trans-Golgi network, recycling endosomes, or a growing assortment of stations along the cellular trafficking pathway. The nature of the specific sorting signal and the mechanism through which it is interpreted can influence the route a protein takes through the cell. Cell type-specific variations in the targeting motifs of a protein, as are evident for Na,K-ATPase, demonstrate a remarkable capacity to adapt sorting pathways to different developmental states or physiologic requirements. This review summarizes our current understanding of apical and basolateral trafficking routes in polarized epithelial cells.

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“…The strong rectification of these channels allows them to stabilize the membrane potential near the potassium equilibrium potential in excitable cells and glia. At the resting membrane potentials of human RPE, (~−56 mV; Quinn and Miller, 1992), however, Kir2.1, Kir2.2, and Kir2.1/Kir2.2 channels would largely be closed due to voltage-dependent block by intracellular polyamines (Nichols and Lopatin, 1997). Interestingly, strongly inwardly rectifying K + currents consistent with Kir2.1 or Kir2.2 have been observed in cultured human RPE cells (Hughes and Takahira, 1996;Wen et al, 1993).…”

Section: Physiological Significancementioning

confidence: 99%

Expression of inwardly rectifying potassium channel subunits in native human retinal pigment epithelium

Yang

Zhang

Hughes

2008

Experimental Eye Research

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Previously, we demonstrated that the inwardly rectifying K + (Kir) channel subunit Kir7.1 is highly expressed in bovine and human retinal pigment epithelium (RPE). The purpose of this study was to determine whether any of the 14 other members of the Kir gene family are expressed in native human RPE. Conventional reverse transcription-polymerase chain reaction (RT-PCR) analysis indicated that in addition to Kir7.1, 7 other Kir channel subunits (Kir1.1, Kir2.1, Kir2.2, Kir3.1, Kir3.4, Kir4.2 and Kir6.1) are expressed in the RPE, whereas in neural retina, all 14 of the Kir channel subunits examined are expressed. The identities of RT-PCR products in the RPE were confirmed by DNA sequencing. Real-time RT-PCR analysis showed, however, that transcripts of these channels are significantly less abundant than Kir7.1 in the RPE. Western blot analysis of the Kir channel subunits detected in the RPE by RT-PCR revealed the expression of Kir2.1, Kir3.1, Kir3.4, Kir4.2, Kir6.1, and possibly Kir2.2, but not Kir1.1, in both human RPE and neural retina. Our results indicate that human RPE expresses at least 5 other Kir channel subtypes in addition to Kir7.1, suggesting that multiple members of the Kir channel family may function in this epithelium.

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Ion transport mechanisms in human retinal pigment epithelium (RPE)

Cited by 74 publications

References 0 publications

Oxidant and antioxidant modulation of chloride channels expressed in human retinal pigment epithelium

Oxidant and antioxidant modulation of chloride channels expressed in human retinal pigment epithelium

Trafficking to the Apical and Basolateral Membranes in Polarized Epithelial Cells

Expression of inwardly rectifying potassium channel subunits in native human retinal pigment epithelium

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