Abstract
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.
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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 329:134–138
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 91:3505–3509
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 19:5332–5347
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 17:1993–2005
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 275:15135–15141
Broillet MC, Firestein S (1996) Direct activation of the olfactory cyclic nucleotide-gated channel through modification of sulfhydryl groups by NO compounds. Neuron 16:377–385
Busse R, Edwards G, Feletou M, Fleming I, Vanhoutte PM, Weston AH (2002) EDHF: bringing the concepts together. Trends Pharmacol Sci 23:374–380
Cohen RA, Vanhoutte PM (1995) Endothelium-dependent hyperpolarization. Beyond nitric oxide and cyclic GMP. Circulation 92:3337–3349
Dhallan RS, Yau KW, Schrader KA, Reed RR (1990) Primary structure and functional expression of a cyclic nucleotide-activated channel from olfactory neurons. Nature 347:184–187
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–C1344
Distler M, Biel M, Flockerzi V, Hofmann F (1994) Expression of cyclic nucleotide-gated cation channels in non-sensory tissues and cells. Neuropharmacology 33:1275–1282
Fesenko EE, Kolesnikov SS, Lyubarsky AL (1985) Induction by cyclic GMP of cationic conductance in plasma membrane of retinal rod outer segment. Nature 313:310–313
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 74:1333–1345
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 15:169–179
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 254:730
Haynes L, Yau KW (1985) Cyclic GMP-sensitive conductance in outer segment membrane of catfish cones. Nature 317:61–64
Kaupp UB (1995) Family of cyclic nucleotide gated ion channels. Curr Opin Neurobiol 5:434–442
Kaupp UB, Seifert R (2002) Cyclic nucleotide-gated ion channels. Physiol Rev 82:769–824
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 342:762–766
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 93:10440–10445
Kingston PA, Zufall F, Barnstable CJ (1999) Widespread expression of olfactory cyclic nucleotide-gated channel genes in rat brain: implications for neuronal signaling. Synapse 32:1–12
Liman ER, Buck LB (1994) A second subunit of the olfactory cyclic nucleotide-gated channel confers high sensitivity to cAMP. Neuron 13:611–621
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 91:1421–1430
Nakamura T, Gold GH (1987) A cyclic nucleotide-gated conductance in olfactory receptor cilia. Nature 325:442–444
Nilius B, Droogmans G (2001) Ion channels and their functional role in vascular endothelium. Physiol Rev 81:1415–1459
Samanta Roy DR, Barnstable CJ (1999) Temporal and spatial pattern of expression of cyclic nucleotide-gated channels in developing rat visual cortex. Cereb Cortex 9:340–347
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 368:859–863
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 275:18887–18896
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 41:282–290
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–C1089
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This study was supported by Hong Kong Research Grant Council (CUHK4174/02 M) and Chinese University Research Committee Funding.
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Cheng, KT., Chan, F.L., Huang, Y. et al. Expression of olfactory-type cyclic nucleotide-gated channel (CNGA2) in vascular tissues. Histochem Cell Biol 120, 475–481 (2003). https://doi.org/10.1007/s00418-003-0596-2
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DOI: https://doi.org/10.1007/s00418-003-0596-2