Chapter 2 Retinal pigment epithelial cell contributions to the electroretinogram and electrooculogram

Steinberg, Roy H.; Linsenmeier, Robert A.; Griff, Edwin R.

doi:10.1016/0278-4327(85)90004-5

Cited by 102 publications

(105 citation statements)

References 52 publications

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“…Others have suggested that the increase in the basal RPE Cl conductance associated with the electrooculogram light peak is triggered by an intracellular second messenger, with Ca 2ϩ being one of the possibilities (9,10). To examine whether the hBest1 channels are sensitive to intracellular Ca 2ϩ , hBest1-transfected 293 cells were loaded with the photolyzable caged-Ca 2ϩ compound, Ca 2ϩ -NPEGTA (17), from a wholecell pipette, and the effect of a flash on the voltage-clamp current was measured.…”

Section: Resultsmentioning

confidence: 99%

The vitelliform macular dystrophy protein defines a new family of chloride channels

Sun

Tsuruo

Yau³

et al. 2002

Proc. Natl. Acad. Sci. U.S.A.

424

427

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Vitelliform macular dystrophy (VMD͞Best disease; MIM*153700) is an early-onset autosomal dominant disorder in which accumulation of lipofuscin-like material within and beneath the retinal pigment epithelium is associated with a progressive loss of central vision. Bestrophin, the protein product of the VMD gene, has four predicted transmembrane domains. There are multiple bestrophin homologues in the human, Drosophila, and Caenorhabditis elegans genomes, but no function has previously been ascribed to these proteins, and they show no detectable homology to other proteins of known function. Using heterologous expression, we show here that human, Drosophila, and C. elegans bestrophins form oligomeric chloride channels, and that human bestrophin is sensitive to intracellular calcium. Each of 15 missense mutations asscociated with VMD greatly reduces or abolishes the membrane current. Four of these mutant bestrophins were coexpressed with the wild type and each dominantly inhibited the wild-type membrane current, consistent with the dominant nature of the disease. These experiments establish the existence of a new chloride channel family and VMD as a channelopathy.

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Section: Resultsmentioning

confidence: 99%

The vitelliform macular dystrophy protein defines a new family of chloride channels

Sun

Tsuruo

Yau³

et al. 2002

Proc. Natl. Acad. Sci. U.S.A.

424

427

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“…Following the relatively rapid a-and b-waves, which reflect primarily the activity of photoreceptors and bipolar cells, respectively (Robson et al 2003;Robson and Frishman 1995), the ERG is known to include a series of slow potentials that are generated in response to neural activity by nonneuronal elements of the retina (Steinberg et al 1985). The positive polarity c-wave occurs within several seconds following a light stimulus and represents the sum of two potentials that are generated in response to the light-induced decline in subretinal [K ϩ ].…”

Section: Introductionmentioning

confidence: 99%

Light-Evoked Responses of the Mouse Retinal Pigment Epithelium

Wu¹,

Peachey²,

Marmorstein³

2004

Journal of Neurophysiology

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In response to light, the retinal pigment epithelium (RPE) generates a series of slow potentials that can be recorded as the c-wave, fast oscillation (FO), and light peak (LP) of the electroretinogram (ERG). As these potentials can be related to specific cellular events, they provide information about RPE function and how that may be altered by disease or experimental manipulation. In the present study we describe a noninvasive means for recording the light-evoked responses of the mouse RPE and use this to define the stimulus-response properties of the major components in three inbred strains of mice (BALBc/ByJ, C57BL/6J, and 129/SvJ) and two mouse mutants that reduce activity in the rod pathway. All of the major ERG components generated by the RPE are readily measured in the mouse. In albino strains (BALBc/ByJ and 129/SvJ) the intensity-response functions for the c-wave, FO, and LP are shifted toward lower intensities in comparison to those for C57BL/6J mice. Each of these components was markedly reduced in mice lacking transducin in which rod phototransduction is interrupted, indicating that they reflect primarily rod photoreceptor activity. All components were observed in no b-wave ( nob) mutant mice, indicating that inner retinal activity does not make a major contribution to these potentials. Further studies of mutant mice will allow us to define the functional consequences of gene manipulation on RPE function and to evaluate specific hypotheses regarding the generation of ERG components.

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“…These conductances are of fundamental importance to RPE cell physiology, since they underlie the changes in apical membrane potential and transepithelial potential produced by the decrease in the extracellular potassium concentration that follows a light flash (Schmidt and Steinberg, 1971;Steinberg et al, 1980;Oakley, 1983). These changes in potential are responsible for the generation of the retinal C=wave (Marmor and Lurie, 1979;Steinberg et al, 1985). These conductances may also be important for the role of the RPE cells in regulating the ionic environment of the photoreceptors (Miller and Steinberg, 1982;Steinberg et al, 1983;Immel and Steinberg, 1986;La Cour et al, 1986).…”

Section: Potassium Permeability Of Rpementioning

confidence: 99%

“…The retinal pigment epithelium (RPE) is a transporting epithelium that plays an important role in the local regulation of ions and metabolites in the interphotoreceptor space, that is, the space that separates the apical RPE membrane from the rod outer segments (Steinberg and Miller, 1979;Steinberg et al, 1985). The basal membrane of the RPE is near the blood-vessel-rich choroid, and the processes of the RPE apical membrane surround the rod outer segments.…”

Section: Introductionmentioning

confidence: 99%

Single-channel recordings from cultured human retinal pigment epithelial cells.

Fox

Pfeffer

Fain

1988

The Journal of General Physiology

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We have applied patch-clamp techniques to on-cell and excisedmembrane patches from human retinal pigment epithelial cells in tissue culture. Single-channel currents from at least four ion channel types were observed: three or more potassium-selective channels with single-channel slope conductances near 100, 45, and 25 pS as measured in on-cell patches with physiological saline in the pipette, and a relatively nonselective channel with subconductance states, which has a main-state conductance of ~300 pS at physiological ion concentrations. The permeability ratios, PK/PNa, measured in excised patches were 21 for the 100-pS channels, 3 for the 25-pS channels, and 0.8 for the 300-pS nonselective channel. The 45-pS channels appeared to be of at least two types, with PK/PN~'S of--4 1 for one type and 3 for the other. The potassiumselective channels were spontaneously active at all potentials examined. The average open time for these channels ranged from a few milliseconds to many tens of milliseconds. No consistent trend relating potassium-selective channel kinetics to membrane potential was apparent, which suggests that channel activity was not regulated by the membrane potential. In contrast to the potassium-selective channels, the activity of the nonselective channel was voltage dependent: the open probability of this channel declined to low values at large positive or negative membrane potentials and was maximal near zero. Singlechannel conductances observed at several symmetrical KCI concentrations have been fitted with Michaelis-Menten curves in order to estimate maximum channel conductances and ion-binding constants for the different channel types. The channels we have recorded are probably responsible for the previously observed potassium permeability of the retinal pigment epithelium apical membrane.

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Chapter 2 Retinal pigment epithelial cell contributions to the electroretinogram and electrooculogram

Cited by 102 publications

References 52 publications

The vitelliform macular dystrophy protein defines a new family of chloride channels

The vitelliform macular dystrophy protein defines a new family of chloride channels

Light-Evoked Responses of the Mouse Retinal Pigment Epithelium

Single-channel recordings from cultured human retinal pigment epithelial cells.

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