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Basal Calcium Entry in Retinal Pigment Epithelial Cells Is Mediated by TRPC Channels

¹From the Experimentelle Ophthalmologie, Klinik und Poliklinik für Augenheilkunde, Universitätsklinkikum Hamburg-Eppendorf, Hamburg, Germany; and the ²Experimentelle Ophthalmologie, Klinik und Poliklinik für Augenheilkunde, Klinikum der Universität Regensburg, Regensburg, Germany.

PURPOSE. Ca²⁺ is a major regulator of cell function. In the retinal pigment epithelium (RPE), intracellular free Ca²⁺ concentration ([Ca²⁺]_i) is essential for the maintenance of normal retinal function. Therefore, accurate control of [Ca²⁺]_i is vital in these cells. Because Ca²⁺ is permanently extruded from the cytosol, RPE cells need a basal Ca²⁺ entry pathway that counteracts this Ca²⁺ efflux. The purpose of this study was to identify the molecular basis of basal Ca²⁺ entry into the RPE.

METHODS. [Ca²⁺]_i was measured using Fura-2–loaded ARPE-19 cells. The expression pattern of TRPC channels was investigated by RT-PCR with RNA extracted from ARPE-19 cells and freshly isolated RPE cells from human donor eyes.

RESULTS. In most cells, basal [Ca²⁺]_i is highly controlled by cell membranes that are only slightly permeable to Ca²⁺ and by the activity of Ca²⁺ pumps and transporters. The authors show here that RPE cells have a basal Ca²⁺ conductance that is dose dependently blocked by La³⁺. Basal [Ca²⁺]_i was also strongly reduced by the TRP channel blockers Gd³⁺, Ni²⁺, 2-APB, and SKF96365 and was insensitive to blockers of other Ca²⁺ channels. In confirmation of this pharmacologic profile, RPE cells expressed TRPC1 and TRPC4 channels, as shown by RT-PCR experiments.

CONCLUSIONS. Ca²⁺ is needed for several permanently occurring regulatory processes in RPE cells. The Ca²⁺ influx pathway identified in this study is essential to define a resting basal [Ca²⁺]_i. This resting [Ca²⁺]_i may contribute, for example, to basal cytokine secretion essential for the maintenance of normal retinal function.