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Hanna Heikkinen, Teemu Turunen, Frans Vinberg, Ari Koskelainen; Sensitivity Regulation In Mouse Cones Expressing Human Red Opsin. Invest. Ophthalmol. Vis. Sci. 2012;53(14):744.
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© ARVO (1962-2015); The Authors (2016-present)
Studying cone phototransduction in the mouse is complicated by the dominant presence of rods: the rod signals need to be extinguished either by saturating lights (which may also affect cones and /or fail to suppress all rod function) or by using genetically manipulated animal models in which rods are absent (e.g. Rho-/-) or non-responsive to light (rod α-transducin knockout, gnat1-/-). In the latter approach, it has not been established to what extent the obtained results correspond to cone function in the WT retina. The aim of this study is to characterize the gain control mechanisms of cones in an intact retina with normal complement of functioning rods.
Cone light responses were isolated from the combined photoreceptor response of the transretinal electroretinogram with rod-saturating preflashes, after blocking synaptic transmission with DL-APB/DNQX. The responses were recorded from wild-type retinas and from retinas with the X-linked mouse green pigment gene replaced with the human red (L-)pigment (Smallwood et al., PNAS 100:11706-11). The mice hemizygous for the mutation allowed spectral separation of the rod and (L-)cone light responses, ensuring that the cone responses were not contaminated by rods. Light adaptation of the L-cones was studied with steps of 685-730 nm background light. This minimized rod desensitization and bleaching to help the preflashes maintain their capacity to saturate rods.
The flash responses of dark- and light-adapted M- (WT) and L-cones (GM) were similar in sensitivity and kinetics, the red-shifted absorption spectrum appearing as the only functional difference between the genotypes. Under experimental conditions previously optimized for physiological and stable rod function, the dark-adapted cone responses peaked at ca. 50 ms, close to the estimates from corneal ERG (Shirato et al, 2008, Exp Eye Res 86:914-28). The flash responses showed prototypical recovery acceleration, combined with response compression and desensitization when retinas were adapted with steps of background light. However, the dominant time constant characterizing the timing of saturated response recovery, ca. 30 ms, remained constant during light-adaptation.
Sensitivity regulation of mouse cones can be conveniently studied from the intact retina using a mouse model with spectrally distinguishable rods and cones. The cones expressing human red opsin correspond physiologically to wild-type cones and appear similar in kinetics to other mammalian cones. Our results suggest that the molecular factor underlying the dominant time constant of flash response recovery does not contribute to the gain control of these cones during short timescale light-adaptation.
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