Artikel
L-type Ca2+ channels in the retinal pigment epithelium: differences in the expression pattern between ARPE-19 cells and RPE cells from patients with choroidal neovascularization
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Autoren
Veröffentlicht: | 22. September 2004 |
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Gliederung
Text
Objective
Secretion of various growth factors by the retinal pigment epithelium (RPE) is substantial for normal structure of the retina but also plays a role in the etiology of retinal diseases. Further, the RPE itself is the target of cytokines. L-type Ca2+ channels are mediating intracellular processing from incoming signals and subsequent growth factor secretion. Purpose of this study was to resolve the molecular structure of the Ca2+ channels expressed by the RPE and to compare it to those of patients with choroidal neovascularization (CNV).
Methods
The biophysical properties of Ca2+ currents in the RPE were investigated by the patch-clamp technique. The complete coding sequence of the pore forming α subunit of the human RPE cell line ARPE-19 and from patients with CNV was cloned and the expression pattern of accessory subunits was investigated by RT-PCR.
Results
The RPE from patients with CNV show Ba2+ currents similar to the Ba2+ currents in ARPE-19 cells. Both were reduced by the specific inhibitor nifedipine and stimulated by BayK 8644. The currents displayed unusual fast inactivation kinetics. We found differences between ARPE-19 cells and CNV in the pore forming α subunit Cav1.3 as well as in the expression pattern of the accessory Ca2+ channel subunits.
Conclusions
The Ba2+ currents we found in RPE cells displayed dihydropyridine sensitivities like neuroendocrine Ca2+ channels. Consistently, we revealed the splice-variant of the Cav1.3 α subunit expressed in the RPE. The obvious differences in the inactivation kinetics between neuroendocrine Ca2+ channels in the RPE and other cells may be explained by a yet unknown regulation mechanism of the channels in the RPE. These differences may be caused by the expression of the splicing variant and the expression pattern of accessory subunits.