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L. A. Cervetto, L. Della Santina, C. M. Gargini, I. Piano, L. Cangiano, S. Asteriti, A. Ludwig; Analysis of the Erg Response in Hcn-1 and Hcn-2 Knock-Out Mice. Invest. Ophthalmol. Vis. Sci. 2010;51(13):1070.
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Hyperpolarization cyclic nucleotide-activated channels (HCN) are widely distributed within the various retinal neurons where they are expressed as HCN1-4 isoforms. Although their functional role is still unclear, converging evidence suggests that they take part in setting appropriate kinetic parameters for the temporal accuracy of salient visual signals. In the present study we compare the functional properties of wild type (wt), HCN-1 and HCN-2 deficient mice.
Electroretinogram (ERG) was recorded from intact anaesthetized animals in response to a variety of light stimuli. Data obtained from wild type (wt) in control and after HCN inhibition were compared with those recorded from HCN1 and HCN2 deficient mice. The relative contribution of cone and rod pathway was dissected using a paired flash paradigm. Frequency Response Curves (FRC) were obtained by plotting the amplitude of the response as a function of the temporal frequency of sinusoidal luminance changes. Retinal distribution and isoform identification of the HCN were assessed by immunohistochemistry.
The most striking feature of HCN inhibition on the ERG response was observed by analyzing the FRC that in control wt shifted from a band-pass mode with a resonant peak at 2Hz in to a low-pass mode after HCN blockade. The FRCs obtained from HCN1 and HCN2 genetically deleted mice were intermediate between a band-and a low-pass profile with the resonant peak shifted to a lower frequency. HCN pharmacological inhibition in these deficient mice caused a full transition of the FRCs to a low-pass profile. HCN-1 deficient mice have a normal rod b-wave while the cone component is substantially reduced, at variance with the HCN-2 deficient mice where the amplitude of the rod b-wave is significantly reduced but the cone component is normal.
These observations confirm and extend the notion that gating of retinal HCN channels controls the kinetics of the light response. In addition they show that genetic HCN deletion affects also other functional properties that depend from the missing isoform.
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