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Acta Physiologica 2007; Volume 190, Supplement 655
XXXIV Congress of The Spanish Society for Physiological Sciences
7/3/2007-7/7/2007
Valladolid, Spain
INFLUENCE OF BESTROPHIN-1 ON INTRACELLULAR SIGNAL TRANSDUCTION IN THE RETINAL PIGMENT EPITHELIUM
Abstract number: S32
Strauss1 O, Krejcova1 S, Neussert1 R, Karl1 M, Striessnig1 J, Wimmers1 S
1Experimentelle Ophthalmologie Klinik und Poliklinik fr Augenheilkunde, Universittsklinikum Hamburg-Eppendorf; Martinistrasse 52, 20246 Hamburg, Germany
Mutations in the VMD2 gene cause Best's vitelliforme macular dystrophy. The VMD2 Bestrophin-1 was so far functionally characterised as calcium-dependent chloride channel. A model in which mutations lead to a loss of this function is challenged by clinical observations and by observations in VMD2 knock-out mice. Purpose of the study is to identify other functions of bestrophin-1 which might help to understand the clinical heterogenous picture. Methods: Investigation of retinal pigment epithelial (RPE) cells from Vmd2-/- mice, heterologeous expression, calcium imaging, immunoprecipitation, patch-clamp. RPE cells functionally express L-type calcium channel of the neuro-endrocrine subtype (Cav1.3 subunits). Transient transfection of these cells with bestrophin-1 led to changes L-type channel characteristics: faster activation kinetics and a shift in the voltage-dependent activation. Bestrophin-1 W93C and R218C shifted the voltage-dependence in the same manner but had different effects of L-type channel kinetics. No co-immunoprecipitation with the Cav1.3 subunit and bestrophin-1 but co-immunoprecipitation with the auxiliary beta-3 subunit and bestrophin-1 were observed. To explore further the subsequent effects on intracellular calcium signalling we investigated ATP-induced calcium transients in RPE cells from wild-type and Vmd2-/- mice. Here, we could detect larger calcium signals which stem from release of calcium from cytosolic stores. This seems to be in accordance with observations that a larger part of bestrophin-1 was often detected in the cytosol. Our data suggest additional function of bestrophin-1 to that of a chloride channel which enables the functional modulation of calcium channels and calcium signalling in a more general manner. Supported DFG STR480/9-1
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Acta Physiologica 2007; Volume 190, Supplement 655 :S32