Journal article
Functional consequences of progressive cone dystrophy-associated mutations in the human cone photoreceptor cyclic nucleotide-gated channel CNGA3 subunit
American Journal of Physiology: Cell Physiology, Vol.289(1), pp.C187-198
07/2005
Handle:
https://hdl.handle.net/2376/101539
PMID: 15743887
Abstract
Progressive cone dystrophies are a genetically heterogeneous group of disorders characterized by early deterioration of visual acuity and color vision, together with psychophysical and electrophysiological evidence of abnormal cone function and cone degeneration. Recently, three mutations in the gene encoding the CNGA3 subunit of cone photoreceptor cyclic nucleotide-gated (CNG) channels have been linked to progressive cone dystrophy in humans. To investigate the functional consequences of these mutations, we expressed mutant human CNGA3 subunits in Xenopus oocytes, alone or together with human CNGB3, and studied these channels using patch-clamp recording. Compared with wild-type channels, homomeric and heteromeric channels containing CNGA3-N471S or CNGA3-R563H subunits exhibited an increase in apparent affinity for cGMP and an increase in the relative agonist efficacy of cAMP compared with cGMP. In contrast, R277C subunits did not form functional homomeric or heteromeric channels. Cell surface expression levels, determined using confocal microscopy of green fluorescent protein-tagged subunits and patch-clamp recording, were significantly reduced for both R563H and R277C but unchanged for N471S. Overall, these results suggest that the plasma membrane localization and gating properties of cone CNG channels are altered by progressive cone dystrophy-associated mutations, providing evidence that supports the pathogenicity of these mutations.
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Details
- Title
- Functional consequences of progressive cone dystrophy-associated mutations in the human cone photoreceptor cyclic nucleotide-gated channel CNGA3 subunit
- Creators
- Chunming Liu - Department of Veterinary and Comparative Anatomy, Pharmacology, and Physiology and Program in Neuroscience, Washington State University, PO Box 646520, Pullman, Washington 99164-6520, USAMichael D Varnum
- Publication Details
- American Journal of Physiology: Cell Physiology, Vol.289(1), pp.C187-198
- Academic Unit
- Integrative Physiology and Neuroscience, Department of
- Publisher
- United States
- Grant note
- R01 EY-12836 / NEI NIH HHS
- Identifiers
- 99900546560301842
- Language
- English
- Resource Type
- Journal article