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C-subfamily ATP binding cassette transporters extrude the calcium fluorescent probe fluo-4 from a cone photoreceptor cell line

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Abstract

Whole transcriptome sequencing has revealed the existence of mRNAs for multiple membrane transporters in photoreceptors. Except for ATP binding cassette (ABC) member A4, involved in the retinoid cycle, an understanding of the function of most transport proteins in photoreceptors is lacking. In this research paper, extrusion of fluo-4, a Ca2+ fluorescent probe, from 661W cells, a cone photoreceptor murine cell line was studied with online fluorometry and immunocytochemistry. Fluo-4 efflux was temperature dependent, required ATP but not extracellular Na+, was not affected by pH in the range 5.4–8.4, and followed saturating kinetics with a Km of nearly 4 μM, suggesting it was effected by ABC type transporters. A panel of antagonists showed an inhibitory profile typical of the C subfamily of ABC transporters. Immunofluorescence staining was positive for ABCC3, ABCC4 and ABCC5. These experimental results are compatible with fluo-4 being extruded from 661W cones by one or a combination of C-type ABC transporters. Examination of physicochemical descriptors related to drug membrane permeability and ABC substrate binding region further suggested efflux of fluo-4 by C-type ABC transporters. Possible functions of this transport mechanism in photoreceptors are discussed.

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Abbreviations

ABC:

ATP binding cassette transporter

F4:

Fluo-4

F4-AM:

Fluo-4 acetoxymethylester

PR:

Photoreceptor

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Funding

This study was financially supported by the Instituto Teófilo Hernando.

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  1. Instituto Teófilo Hernando de I+D del Medicamento, Madrid, Spain

    Antonio-Miguel García-de-Diego

  2. Departamento de Farmacología y Terapéutica, Facultad de Medicina, Universidad Autónoma de Madrid, Madrid, Spain

    Antonio-Miguel García-de-Diego

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AMGD performed the experiments and wrote the manuscript. All authors reviewed the manuscript.

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García-de-Diego, AM. C-subfamily ATP binding cassette transporters extrude the calcium fluorescent probe fluo-4 from a cone photoreceptor cell line. Naunyn-Schmiedeberg's Arch Pharmacol 396, 1727–1740 (2023). https://doi.org/10.1007/s00210-023-02422-8

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