In:
The Journal of Neuroscience, Society for Neuroscience, Vol. 28, No. 45 ( 2008-11-05), p. 11662-11672
Kurzfassung:
The G90D rhodopsin mutation is known to produce congenital night blindness in humans. This mutation produces a similar condition in mice, because rods of animals heterozygous (D+) or homozygous (D+/+) for this mutation have decreased dark current and sensitivity, reduced Ca 2+ , and accelerated values of τ REC and τ D , similar to light-adapted wild-type (WT) rods. Our experiments indicate that G90D pigment activates the cascade, producing an equivalent background light of ∼130 Rh* rod −1 for D+ and 890 Rh* rod −1 for D+/+. The active species of the G90D pigment could be unregenerated G90D opsin or G90D rhodopsin, either spontaneously activated (as Rh*) or in some other form. Addition of 11- cis -retinal in lipid vesicles, which produces regeneration of both WT and G90D opsin in intact rods and ROS membranes, had no effect on the waveform or sensitivity of dark-adapted G90D responses, indicating that the active species is not G90D opsin. The noise spectra of dark-adapted G90D and WT rods are similar, and the G90D noise variance is much less than of a WT rod exposed to background light of about the same intensity as the G90D equivalent light, indicating that Rh* is not the active species. We hypothesize that G90D rhodopsin undergoes spontaneous changes in molecular conformation which activate the transduction cascade with low gain. Our experiments provide the first indication that a mutant form of the rhodopsin molecule bound to its 11- cis -chromophore can stimulate the visual cascade spontaneously at a rate large enough to produce visual dysfunction.
Materialart:
Online-Ressource
ISSN:
0270-6474
,
1529-2401
DOI:
10.1523/JNEUROSCI.4006-08.2008
Sprache:
Englisch
Verlag:
Society for Neuroscience
Publikationsdatum:
2008
ZDB Id:
1475274-8
SSG:
12
