December 2002
Volume 43, Issue 13
Free
ARVO Annual Meeting Abstract  |   December 2002
The Nucleotide Binfing Domain of the ß Subunit of Human Rod Cyclic Nucleotide-Gated Channels (CNG4) is Activated by 12-Fold Lower Concentrations of cAMP Than the Nucleotide Binding Domain of the Bovine Rod Subunit (CNG1) in Chimeric CNG Channels
Author Affiliations & Notes
  • G Woch
    Department of Biology Center for Biotechnology Temple University Philadelphia PA
  • JQ Zheng
    Department of Biology Center for Biotechnology Temple University Philadelphia PA
  • SP Scott
    Department of Biology Center for Biotechnology Temple University Philadelphia PA
  • JC Tanaka
    Department of Biology Center for Biotechnology Temple University Philadelphia PA
  • Footnotes
    Commercial Relationships   G. Woch, None; J.Q. Zheng, None; S.P. Scott, None; J.C. Tanaka, None. Grant Identification: Support: NIH Grant EY06640
Investigative Ophthalmology & Visual Science December 2002, Vol.43, 3756. doi:
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      G Woch, JQ Zheng, SP Scott, JC Tanaka; The Nucleotide Binfing Domain of the ß Subunit of Human Rod Cyclic Nucleotide-Gated Channels (CNG4) is Activated by 12-Fold Lower Concentrations of cAMP Than the Nucleotide Binding Domain of the Bovine Rod Subunit (CNG1) in Chimeric CNG Channels . Invest. Ophthalmol. Vis. Sci. 2002;43(13):3756.

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

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Abstract

Abstract: : Purpose: The human rod CNG4 does not express in the absence of CNG1, so its nucleotide activation properties have not been characterized. We characterized the nucleotide activation properties of the nucleotide-binding domain of CNG4 using a CNG chimera construct with the N-terminus from CNG2, the α subunit of the olfactory CNG channel. Methods: Nucleotide-activated currents were recorded from excised membrane patches of tSA201 cells expressing a chimeric CNG channel. The control chimera, Χα, was constructed with the N-terminal region of CNG2 from the olfactory CNG channel and the nucleotide binding domain from CNG1. Χß was constructed in the same manner with the nucleotide binding domain from CNG4. Results: Χß was activated by lower concentrations of both cGMP and cAMP than Χα. The K0.5 values for Χß were 0.81 ± 0.05 µM (n=7) and 78.4 ± 5.1 µM (n=6) for cGMP and cAMP, respectively, with Hill coefficients of 2.7 ± 0.46 and 1.5 ± 0.16. Comparable values for Χα were 4.2 ± 0.63 µM (n=9) and 963 ± 381 µM (n=9) for cGMP and cAMP with Hill coefficients of 1.4 ± 0.12 and 1.34 ± 0.10. In both chimeras, cAMP was a full agonist. Therefore, in identical CNG channel constructs, the ß binding domain confers a 5-fold lower activation for cGMP and a 12-fold lower activation for cAMP than the α binding domain. Conclusion: In native rod channels, cAMP is a weak, partial agonist with the ability to potentiate cGMP-activated currents at concentrations of cGMP in the range of dark-adapted rods. The increased cAMP sensitivity of the ß nucleotide binding-domain might confer on heteromeric CNG channels the ability to relay signals from both cGMP and cAMP. Given the role of cAMP in the photoreceptor circadian clock, a novel possibility is that photoreceptor CNG channels transduce information about photoperiod through CNG channels.

Keywords: 394 electrophysiology: non-clinical • 445 ion channels • 517 photoreceptors 
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