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B. Lei, K. Zhang, G. Yao, X. Fan, N. L. Hawes, B. Chang; Supernormal Dark-Adapted Electroretinogram b-wave in Hyperpolarization-Activated Cyclic Nucleotide-Gated Channel 1 (HCN1) Knockout Mice. Invest. Ophthalmol. Vis. Sci. 2007;48(13):1938.
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© ARVO (1962-2015); The Authors (2016-present)
The hyperpolarization-activated cyclic nucleotide-gated cation channel 1 (HCN1) has been identified in the inner segment of rod photoreceptors and a subtype of OFF-type cone bipolar cells. Increasing evidence suggested that HCN1 may play important roles in modulating the visual signal processing and transmission in the retina. We studied electroretinogram (ERG) of the HCN1 knockout (HCN1-/-) mice.
Ten 6-week-old HCN1-/- mice and seven age-matched wild type C57BL/6J mice were used. One micro liter of CsCl solution (a HCN1 blocker) was injected into the vitreous of another group of wild type mice (n=7). Dark- and light-adapted ERG, dark-adapted 10 Hz flicker ERG were recorded. The range of the stimulus light intensity covered 5 log units with the highest intensity of 0.6 log cd-s/m2. For light-adapted ERG, the mice were exposed to a rod suppressing background of 30 cd/m2. Ratios of dark-adapted ERG b-wave vs. a-wave were determined. ERG oscillatory potentials (OPs) were extracted with a digital filter and OP frequency spectra were analyzed with fast Fourier transform. The peak frequency and total energy of the OP were estimated.
HCN1-/- mice showed increased dark-adapted ERG b-wave (p<0.01) and decreased a-wave (p<0.01) amplitudes compared to the wild type mice. An increased b-wave vs. a-wave ratio was evident in HCN1-/- mice (3.3 vs. 1.9. p<0.001). Ironically, despite the elevated ERG b-wave, the total OP energy of the HCN1-/- mice significantly decreased (p<0.01). The light-adapted ERGs still can be detected but the b-wave amplitudes were only about 20% of the wildtype controls. The dark-adapted 10 Hz flicker ERG of HCN1-/- mice were normal at low stimulus intensities (-4.35 ~ -2.35 log cd-s/m2) but were significantly smaller than the controls from the middle to higher intensities (>-2.15 log cd-s/m2). ERGs of the CsCl-injected wild type mice were similar to those of the HCN1-/- mice.
Supernormal dark-adapted ERG b-wave, severely decrease of cone system functions and reduce of OP responses are prominent in the HCN1-/- mice. The ERG phenotype of the HCN1-/- mice mimics that observed in a group of cone dystrophy patients. Our results indicate that HCN1 is vital for maintaining normal retinal function, especially under photopic and mesopic luminance conditions.
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