March 2012
Volume 53, Issue 14
Free
ARVO Annual Meeting Abstract  |   March 2012
The Functional and Structural Differences between the Heteromeric and Homomeric CNG Channel in Cone Photoreceptors
Author Affiliations & Notes
  • Xi-Qin Ding
    Cell Biology, Univ Oklahoma Hlth Sciences Ctr, Oklahoma City, Oklahoma
  • Jianhua Xu
    Cell Biology, Univ Oklahoma Hlth Sciences Ctr, Oklahoma City, Oklahoma
  • Arjun Thapa
    Cell Biology, Univ Oklahoma Hlth Sciences Ctr, Oklahoma City, Oklahoma
  • Lynsie Morris
    Cell Biology, Univ Oklahoma Hlth Sciences Ctr, Oklahoma City, Oklahoma
  • Hongwei Ma
    Cell Biology, Univ Oklahoma Hlth Sciences Ctr, Oklahoma City, Oklahoma
  • Jin-Shan Wang
    Department of Ophthalmology and Visual Sciences, Washington University School of Medicine, Saint Louis, Missouri
  • Vladimir Kefalov
    Department of Ophthalmology and Visual Sciences, Washington University School of Medicine, Saint Louis, Missouri
  • Footnotes
    Commercial Relationships  Xi-Qin Ding, None; Jianhua Xu, None; Arjun Thapa, None; Lynsie Morris, None; Hongwei Ma, None; Jin-Shan Wang, None; Vladimir Kefalov, None
  • Footnotes
    Support  This work was supported by grants from the National Center for Research Resources (P20RR017703) and the National Eye Institute (EY12190, EY019490, EY019312 and EY021126).
Investigative Ophthalmology & Visual Science March 2012, Vol.53, 1614. doi:
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      Xi-Qin Ding, Jianhua Xu, Arjun Thapa, Lynsie Morris, Hongwei Ma, Jin-Shan Wang, Vladimir Kefalov; The Functional and Structural Differences between the Heteromeric and Homomeric CNG Channel in Cone Photoreceptors. Invest. Ophthalmol. Vis. Sci. 2012;53(14):1614.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract
 
Purpose:
 

Cone cyclic nucleotide-gated (CNG) channel is a heteromeric complex comprising the subunits CNGA3 and CNGB3. Mutations in CNGB3 account for over 50% of all known cases of achromatopsia. This work investigates the functional and structural differences between the heteromeric and homomeric CNG channels in cones using CNGB3-deficient mouse models.

 
Methods:
 

As cones comprise only 2-3% of the total photoreceptor population in the wild-type mouse retina, we generated the mouse line with CNGB3 deficiency on a cone-dominant background, i.e., CNGB3-/-/Nrl-/- mice. Cone phototransduction was evaluated by photopic electroretinographic (ERG), flicker ERG, and transretinal ERG recordings. CNG channel complex assembly was analyzed by chemical cross-linking and the channel complex stability was evaluated by trypsin-TPCK digestion.

 
Results:
 

CNGB3-/-/Nrl-/- mice showed a 40-50% reduction of the photopic ERG response compared to the age-matched Nrl-/- mice (P30). The flicker ERG responses under photopic conditions were significantly diminished in the CNGB3-/-/Nrl-/- mice. Transretinal ERG recordings showed that the cone sensitivity in CNGB3-/- mice (P30) was about 0.5 log unit lower and the response recovery was about 2.5-fold slower than these of age-matched wild-type mice. Though CNGA3 expression level was much reduced in CNGB3-deficient retina, CNGA3 was able to form the homotetrameric complex in cones. However, the homomeric channel complex was found to be more resistant to trypsin digestion in the experimental conditions used.

 
Conclusions:
 

In the absence of CNGB3, CNGA3 is able to form a functional homomeric channel that maintains cone phototransduction. However, CNGB3 deficiency results in a reduced sensitivity, impaired temporal processing, and slower recovery of the cone light response compared to phototransduction mediated by CNGA3/CNGB3 heteromeric channels.

 
Keywords: ion channels • retina • photoreceptors 
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