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Calcium-dependent chloride conductance in epithelia: is there a contribution by Bestrophin?

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Abstract

Although known for more than 20 years, the molecular identity of epithelial Ca2+-activated Cl− channels remains obscure. Previous candidate proteins did not hold initial promises, and thus, new hope is put into the recently identified family of bestrophin proteins, as they reflect many of the properties found for native channels. Mutations in the bestrophin gene cause an autosomal form of macular dystrophy of the retina. Bestrophin 1 is assumed to form the basolateral Ca2+-activated Cl− channel in the retinal pigment epithelium of the eye. Other data suggest that bestrophin is a regulator of voltage gated Ca2+ channels. Structural information on bestrophins is available and a Cl− selective filter has been localized to the second transmembrane domain of bestrophin. It is possible that bestrophins function as physiologically regulated Cl− channels only in association with additional subunits and auxiliary proteins. Little is known about expression of bestrophin in gland acinar cells, which show a pronounced Ca2+-activated Cl− secretion. In airways and intestinal epithelia, bestrophins could be particularly important in diseases such as cystic fibrosis and secretory diarrhea.

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Acknowledgement

This work is continuously supported by the Deutsche Forschungsgemeinschaft DFG SFB699 A7 and the Else-Kröner-Fresenius-Stiftung. We acknowledge the expert technical assistances by Ms. E. Tartler and Ms. A. Paech. Bestrophins were a generous gift from Prof. Dr. J. Nathans (Howard Hughes Medical Institute, Johns Hopkins University School of Medicine, Baltimore, USA). The C2-toxin and HEK293 cells were kindly provided by Prof. Dr. R. Benz (Biozentrum der Universität Würzburg) and Prof. Dr. R. Witzgall (University of Regensburg, Germany). The GFP-tagged hBest-1 was kindly provided by Prof. Dr. B.H.F. Weber (Institute of Human Genetics, University of Regensburg, Germany).

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  1. Institut für Physiologie, Universität Regensburg, Universitätsstraße 31, 93053, Regensburg, Germany

    Karl Kunzelmann, Vladimir M. Milenkovic, Melanie Spitzner, René Barro Soria & Rainer Schreiber

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Kunzelmann, K., Milenkovic, V.M., Spitzner, M. et al. Calcium-dependent chloride conductance in epithelia: is there a contribution by Bestrophin?. Pflugers Arch - Eur J Physiol 454, 879–889 (2007). https://doi.org/10.1007/s00424-007-0245-z

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