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The light peak of the electroretinogram is dependent on voltage-gated calcium channels and antagonized by bestrophin (best-1)
- Source :
- Journal of General Physiology. May, 2006, Vol. 127 Issue 5, p577, 13 p.
- Publication Year :
- 2006
-
Abstract
- Mutations in VMD2, encoding bestrophin (best-1), cause Best vitelliform macular dystrophy (BMD), adult-onset vitelliform macular dystrophy (AVMD), and autosomal dominant vitreoretinochoroidopathy (ADVIRC). BMD is distinguished fl-om AVMD by a diminished electrooculogram light peak (LP) in the absence of changes in the flash electroretinogram. Although the LP is thought to be generated by best-l, we find enhanced LP luminance responsiveness with normal amplitude in Vmd[2.sup.-/-] mice and no differences in cellular [Cl.sup.-] currents in comparison to Vmd[2.sup.+/+] littermates. The putative [Ca.sup.2+] sensitivity of best-l, and our recent observation that best-1 alters the kinetics of voltage-dependent [Ca.sup.2+] channels (VDCC), led us to examine the role of VDCCs in the LR Nimodipine diminished the LP, leading us to survey VDCC [beta]-subunit mutant mice. Lethargic mice, which harbor a loss of function mutation in the [[beta]sub.4] subunit of VDCCs, exhibited a significant shift in LP luminance response, establishing a role for [Ca.sup.2+] in LP generation. When stimulated with ATE which increases [[[Ca.sup.++]].sub.l], retinal pigment epithelial cells derived from Vmd[2.sup.- /-] mice exhibited a fivefold greater response than Vmd[2.sup.+/+] littermates, indicating that best-1 can suppress the rise in [[[Ca.sup.2+]].sub.1] associated with the LR We conclude that VDCCs regulated by a [[beta].sub.4] subunit are required to generate the LP and that best-1 antagonizes the LP luminance response potentially via its ability to modulate VDCC function. Furthermore, we suggest that the loss of vision associated with BMD is not caused by the same pathologic process as the diminished LP, but rather is caused by as yet unidentified effects of best-1 on other cellular processes.
Details
- Language :
- English
- ISSN :
- 00221295
- Volume :
- 127
- Issue :
- 5
- Database :
- Gale General OneFile
- Journal :
- Journal of General Physiology
- Publication Type :
- Academic Journal
- Accession number :
- edsgcl.146060307