Histochemistry and Cell Biology

, Volume 120, Issue 6, pp 475–481 | Cite as

Expression of olfactory-type cyclic nucleotide-gated channel (CNGA2) in vascular tissues

  • Kwong-Tai Cheng
  • Franky Leung Chan
  • Yu Huang
  • Wing-Yee Chan
  • Xiaoqiang Yao
Original Paper


Cyclic nucleotide-gated (CNG) ion channels are Ca2+-permeable nonselective cation channels that are directly gated by the binding of cAMP or cGMP. Previous studies have identified the expression of CNGA1 channels in vascular endothelial cells. The opening of CNG channels is expected to result in a rise in endothelial cytosolic Ca2+, which may trigger multiple physiological changes. In the present study, we extensively studied the expression pattern of the functional subunit of olfactory-type CNG channels (CNGA2) in vascular tissues. Northern blot analysis detected a transcript of approximately 2.6 kb in mRNA isolated from rat aorta. RT-PCR amplified a 582-bp CNGA2 fragment from RNA samples isolated from rat aorta, bovine endothelia cell CCL-209, and rat smooth muscle cell A7r5. Furthermore, in situ hybridization and immunohistochemistry revealed that CNGA2 mRNA and proteins were expressed in the endothelium and smooth muscle layers of human coronary and cerebral arteries. In conclusion, our study indicates that CNGA2 channels are widely expressed in vascular tissues across different species. These results suggest a potential ubiquitous role of CNGA2 channels in mediating Ca2+ influx in vascular cells.


Gene expression CNGA2 channels Arteries Endothelium Smooth muscle 



This study was supported by Hong Kong Research Grant Council (CUHK4174/02 M) and Chinese University Research Committee Funding.


  1. Biel M, Altenhofen W, Hullin R, Ludwig J, Freichel M, Flockerzi V, Dascal N, Kaupp UB, Hofmann F (1993) Primary structure and functional expression of a cyclic nucleotide-gated channel from rabbit aorta. FEBS Lett 329:134–138CrossRefGoogle Scholar
  2. Biel M, Zong X, Distler M, Bosse E, Klugbauer N, Murakami M, Flockerzi V, Hofmann F (1994) Another member of the cyclic nucleotide-gated channel family, expressed in testis, kidney, and heart. Proc Natl Acad Sci U S A 91:3505–3509PubMedGoogle Scholar
  3. Bonigk W, Bradley J, Muller F, Sesti F, Boekhoff I, Ronnett GV, Kaupp UB, Frings S (1999) The native rat olfactory cyclic nucleotide-gated channel is composed of three distinct subunits. J Neurosci 19:5332–5347PubMedGoogle Scholar
  4. Bradley J, Zhang Y, Bakin R, Lester HA, Ronnett GV, Zinn K (1997) Functional expression of the heteromeric “olfactory” cyclic nucleotide-gated channel in the hippocampus: a potential effector of synaptic plasticity in brain neurons. J Neurosci 17:1993–2005PubMedGoogle Scholar
  5. Broillet MC (2000) A single intracellular cysteine residue is responsible for the activation of the olfactory cyclic nucleotide-gated channel by NO. J Biol Chem 275:15135–15141CrossRefGoogle Scholar
  6. Broillet MC, Firestein S (1996) Direct activation of the olfactory cyclic nucleotide-gated channel through modification of sulfhydryl groups by NO compounds. Neuron 16:377–385PubMedGoogle Scholar
  7. Busse R, Edwards G, Feletou M, Fleming I, Vanhoutte PM, Weston AH (2002) EDHF: bringing the concepts together. Trends Pharmacol Sci 23:374–380PubMedGoogle Scholar
  8. Cohen RA, Vanhoutte PM (1995) Endothelium-dependent hyperpolarization. Beyond nitric oxide and cyclic GMP. Circulation 92:3337–3349PubMedGoogle Scholar
  9. Dhallan RS, Yau KW, Schrader KA, Reed RR (1990) Primary structure and functional expression of a cyclic nucleotide-activated channel from olfactory neurons. Nature 347:184–187CrossRefPubMedGoogle Scholar
  10. Ding C, Potter ED, Qiu W, Coon SL, Levine MA, Guggino SE (1997) Cloning and widespread distribution of the rat rod-type cyclic nucleotide-gated cation channel. Am J Physiol 272:C1335–C1344PubMedGoogle Scholar
  11. Distler M, Biel M, Flockerzi V, Hofmann F (1994) Expression of cyclic nucleotide-gated cation channels in non-sensory tissues and cells. Neuropharmacology 33:1275–1282CrossRefPubMedGoogle Scholar
  12. Fesenko EE, Kolesnikov SS, Lyubarsky AL (1985) Induction by cyclic GMP of cationic conductance in plasma membrane of retinal rod outer segment. Nature 313:310–313Google Scholar
  13. Finn JT, Krautwurst D, Schroeder JE, Chen TY, Reed RR, Yau KW (1998) Functional co-assembly among subunits of cyclic-nucleotide-activated, nonselective cation channels, and across species from nematode to human. Biophys J 74:1333–1345PubMedGoogle Scholar
  14. Frings S, Seifert R, Godde M, Kaupp UB (1995) Profoundly different calcium permeation and blockage determine the specific function of distinct cyclic nucleotide-gated channels. Neuron 15:169–179PubMedGoogle Scholar
  15. Guy HR, Durell SR, Warmke J, Drysdale R, Ganetzky B (1991) Similarities in amino acid sequences of Drosophila eag and cyclic nucleotide-gated channels. Science 254:730PubMedGoogle Scholar
  16. Haynes L, Yau KW (1985) Cyclic GMP-sensitive conductance in outer segment membrane of catfish cones. Nature 317:61–64PubMedGoogle Scholar
  17. Kaupp UB (1995) Family of cyclic nucleotide gated ion channels. Curr Opin Neurobiol 5:434–442CrossRefGoogle Scholar
  18. Kaupp UB, Seifert R (2002) Cyclic nucleotide-gated ion channels. Physiol Rev 82:769–824PubMedGoogle Scholar
  19. Kaupp UB, Niidome T, Tanabe T, Terada S, Bonigk W, Stuhmer W, Cook NJ, Kangawa K, Matsuo H, Hirose T (1989) Primary structure and functional expression from complementary DNA of the rod photoreceptor cyclic GMP-gated channel. Nature 342:762–766PubMedGoogle Scholar
  20. Kingston PA, Zufall F, Barnstable CJ (1996) Rat hippocampal neurons express genes for both rod retinal and olfactory cyclic nucleotide-gated channels: novel targets for cAMP/cGMP function. Proc Natl Acad Sci U S A 93:10440–10445CrossRefPubMedGoogle Scholar
  21. Kingston PA, Zufall F, Barnstable CJ (1999) Widespread expression of olfactory cyclic nucleotide-gated channel genes in rat brain: implications for neuronal signaling. Synapse 32:1–12CrossRefPubMedGoogle Scholar
  22. Liman ER, Buck LB (1994) A second subunit of the olfactory cyclic nucleotide-gated channel confers high sensitivity to cAMP. Neuron 13:611–621PubMedGoogle Scholar
  23. Lincoln TM, Dey N, Sellak H (2001) Invited review: cGMP-dependent protein kinase signaling mechanisms in smooth muscle: from the regulation of tone to gene expression. J Appl Physiol 91:1421–1430PubMedGoogle Scholar
  24. Nakamura T, Gold GH (1987) A cyclic nucleotide-gated conductance in olfactory receptor cilia. Nature 325:442–444PubMedGoogle Scholar
  25. Nilius B, Droogmans G (2001) Ion channels and their functional role in vascular endothelium. Physiol Rev 81:1415–1459PubMedGoogle Scholar
  26. Samanta Roy DR, Barnstable CJ (1999) Temporal and spatial pattern of expression of cyclic nucleotide-gated channels in developing rat visual cortex. Cereb Cortex 9:340–347CrossRefPubMedGoogle Scholar
  27. Weyand I, Godde M, Frings S, Weiner J, Muller F, Altenhofen W, Hatt H, Kaupp UB (1994) Cloning and functional expression of a cyclic-nucleotide-gated channel from mammalian sperm. Nature 368:859–863CrossRefPubMedGoogle Scholar
  28. Wu S, Moore TM, Brough GH, Whitt SR, Chinkers M, Li M, Stevens T (2000) Cyclic nucleotide-gated channels mediate membrane depolarization following activation of store-operated calcium entry in endothelial cells. J Biol Chem 275:18887–18896CrossRefPubMedGoogle Scholar
  29. Yao X, Leung PS, Kwan HY, Wong TP, Fong MW (1999) Rod-type cyclic nucleotide-gated cation channel is expressed in vascular endothelium and vascular smooth muscle cells. Cardiovasc Res 41:282–290CrossRefPubMedGoogle Scholar
  30. Zhang J, Xia SL, Block ER, Patel JM (2002) NO upregulation of a cyclic nucleotide-gated channel contributes to calcium elevation in endothelial cells. Am J Physiol Cell Physiol 283:C1080–C1089PubMedGoogle Scholar

Copyright information

© Springer-Verlag 2003

Authors and Affiliations

  • Kwong-Tai Cheng
    • 1
  • Franky Leung Chan
    • 2
  • Yu Huang
    • 1
  • Wing-Yee Chan
    • 3
  • Xiaoqiang Yao
    • 1
  1. 1.Department of Physiology, Faculty of MedicineChinese University of Hong KongHong KongChina
  2. 2.Department of Anatomy, Faculty of MedicineChinese University of Hong KongHong KongChina
  3. 3.Department of Anatomical and Cellular Pathology, Faculty of MedicineChinese University of Hong KongHong KongChina

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