Expression of bestrophin-1, the product of the VMD2 gene, modulates voltage-dependent Ca2+ channels in retinal pigment epithelial cells
Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Genetics and Pathology2006 (English)In: The FASEB Journal, ISSN 0892-6638, Vol. 20, no 1, 178-80 p.Article in journal (Refereed) Published
Mutations in the VMD2 gene cause Best's disease, an inherited form of macular degeneration. The reduction in the light-peak amplitude in the patient's electro-oculogram suggests that bestrophin-1 influences the membrane conductance of the retinal pigment epithelium (RPE). Systemic application of the L-type Ca2+ channel blocker nimodipine reduced the light-peak amplitude in the rat electroretinogram but not a- and b-waves. Expression of bestrophin-1 in a RPE cell line (RPE-J) led to changes in L-type channel properties. Wild-type bestrophin-1 induced an acceleration of activation kinetics of Ba2+ currents through L-type Ca2+ channels and a shift of the voltage-dependent activation to more negative values, closer to the resting potential of RPE cells. Expression of bestrophin-1 with Best disease-causing mutations led to comparable shifts in voltage-dependent activation but different effects on activation and inactivation kinetics. Bestrophin W93C exhibited slowed activation and inactivation, and bestrophin R218C accelerated the activation and inactivation. Thus, transfection of RPE cells with bestrophin-1 distinctively changed L-type Ca2+ channel kinetics and voltage-dependence. On the basis of these data, we propose that presence of bestrophin-1 influences kinetics and voltage-dependence of voltage-dependent Ca2+ channels and that these effects might open new ways to understand the mechanisms leading to retinal degeneration in Best's disease.
Place, publisher, year, edition, pages
2006. Vol. 20, no 1, 178-80 p.
Medical and Health Sciences
IdentifiersURN: urn:nbn:se:uu:diva-80672DOI: 10.1096/fj.05-4495fjePubMedID: 16282372OAI: oai:DiVA.org:uu-80672DiVA: diva2:108586