© 2001 American Heart Association, Inc.
Cellular Biology |
The Transient Receptor Potential Protein Homologue TRP6 Is the Essential Component of Vascular 
1-Adrenoceptor–Activated Ca2+-Permeable Cation Channel
Presented in part at the 73rd annual meeting of the Japanese Pharmacological Society, Yokohama, Japan, March 24, 2000, and published in abstract form (Jpn J Pharmacol. 2000;82:83P).
From the Department of Pharmacology (R.I., H.O., Y.I.), Graduate School of Medical Sciences, Kyushu University, Fukuoka; Laboratory of Humoral Information (T.O., Y.H., S.S., Y.M.), National Institute for Physiological Sciences, Okazaki, Japan; Department of Pathophysiology School of Pharmaceutical Sciences (S.S.), Showa University, Tokyo; and Tissue and Histopathology Section (S.N.), Division at Scientific Data Registry, Atomic Bomb Disease Institute, Nagasaki University School of Medicine, Japan.
Correspondence to Ryuji Inoue, Department of Pharmacology, Graduate School of Medical Sciences, Kyushu University, Fukuoka 812-8582. E-mail inouery{at}pharmaco.med.kyushu-u.ac.jp
Abstract—The
Drosophila transient receptor
potential protein (TRP) and its mammalian homologues are thought to be
Ca2+-permeable cation channels activated by
G protein (Gq/11)–coupled receptors and are
regarded as an interesting molecular model for the
Ca2+ entry mechanisms associated with
stimulated phosphoinositide turnover and store depletion. However,
there is little unequivocal evidence linking mammalian TRPs with
particular native functions. In this study, we have found that
heterologous expression of murine TRP6 in HEK293 cells reproduces
almost exactly the essential biophysical and pharmacological properties
of 
1-adrenoceptor–activated nonselective
cation channels (1-AR–NSCC) previously
identified in rabbit portal vein smooth muscle. Such properties include
activation by diacylglycerol; S-shaped current-voltage relationship;
high divalent cation permeability; unitary conductance of 25 to 30 pS
and augmentation by flufenamate and Ca2+;
and blockade by Cd2+,
La3+, Gd3+,
SK&F96365, and amiloride. Reverse transcriptase–polymerase chain
reaction and confocal laser scanning microscopy using TRP6-specific
primers and antisera revealed that the level of TRP6 mRNA expression
was remarkably high in both murine and rabbit portal vein smooth
muscles as compared with other TRP subtypes, and the immunoreactivity
to TRP6 protein was localized near the sarcolemmal region of single
rabbit portal vein myocytes. Furthermore, treatment of primary cultured
portal vein myocytes with TRP6 antisense oligonucleotides resulted in
marked inhibition of TRP6 protein immunoreactivity as well as selective
suppression of 1-adrenoceptor–activated,
store depletion–independent cation current and
Ba2+ influx. These results strongly indicate
that TRP6 is the essential component of the
1-AR–NSCC, which may serve as a store
depletion–independent Ca2+ entry pathway
during increased sympathetic
activity.
Key Words: receptor-operated Ca2+ channel • transient receptor potential protein • 1-adrenoceptor
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T. K. Zagranichnaya, X. Wu, and M. L. Villereal Endogenous TRPC1, TRPC3, and TRPC7 Proteins Combine to Form Native Store-operated Channels in HEK-293 Cells J. Biol. Chem., August 19, 2005; 280(33): 29559 - 29569. [Abstract] [Full Text] [PDF]
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 A. Dietrich, M. Mederos y Schnitzler, M. Gollasch, V. Gross, U. Storch, G. Dubrovska, M. Obst, E. Yildirim, B. Salanova, H. Kalwa, et al. Increased Vascular Smooth Muscle Contractility in TRPC6-/- Mice Mol. Cell. Biol., August 15, 2005; 25(16): 6980 - 6989. [Abstract] [Full Text] [PDF]
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M. Freichel, R. Vennekens, J. Olausson, S. Stolz, S. E Philipp, P. Weissgerber, and V. Flockerzi Functional role of TRPC proteins in native systems: implications from knockout and knock-down studies J. Physiol., August 15, 2005; 567(1): 59 - 66. [Abstract] [Full Text] [PDF]
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A. P Albert, A. S Piper, and W. A Large Role of phospholipase D and diacylglycerol in activating constitutive TRPC-like cation channels in rabbit ear artery myocytes J. Physiol., August 1, 2005; 566(3): 769 - 780. [Abstract] [Full Text] [PDF]
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M Liu, A. P Albert, and W. A Large Facilitatory effect of Ins(1,4,5)P3 on store-operated Ca2+-permeable cation channels in rabbit portal vein myocytes J. Physiol., July 1, 2005; 566(1): 161 - 171. [Abstract] [Full Text] [PDF]
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C. S. Facemire and W. J. Arendshorst Calmodulin mediates norepinephrine-induced receptor-operated calcium entry in preglomerular resistance arteries Am J Physiol Renal Physiol, July 1, 2005; 289(1): F127 - F136. [Abstract] [Full Text] [PDF]
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S. A. Reading, S. Earley, B. J. Waldron, D. G. Welsh, and J. E. Brayden TRPC3 mediates pyrimidine receptor-induced depolarization of cerebral arteries Am J Physiol Heart Circ Physiol, May 1, 2005; 288(5): H2055 - H2061. [Abstract] [Full Text] [PDF]
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V. Bugaj, V. Alexeenko, A. Zubov, L. Glushankova, A. Nikolaev, Z. Wang, E. Kaznacheyeva, I. Bezprozvanny, and G. N. Mozhayeva Functional Properties of Endogenous Receptor- and Store-operated Calcium Influx Channels in HEK293 Cells J. Biol. Chem., April 29, 2005; 280(17): 16790 - 16797. [Abstract] [Full Text] [PDF]
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J. P. Vessey, A. K. Stratis, B. A. Daniels, N. Da Silva, M. G. Jonz, M. R. Lalonde, W. H. Baldridge, and S. Barnes Proton-Mediated Feedback Inhibition of Presynaptic Calcium Channels at the Cone Photoreceptor Synapse J. Neurosci., April 20, 2005; 25(16): 4108 - 4117. [Abstract] [Full Text] [PDF]
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 A. B. Parekh and J. W. Putney Jr. Store-Operated Calcium Channels Physiol Rev, April 1, 2005; 85(2): 757 - 810. [Abstract] [Full Text] [PDF]
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A. Bergdahl, M. F. Gomez, A.-K. Wihlborg, D. Erlinge, A. Eyjolfson, S.-Z. Xu, D. J. Beech, K. Dreja, and P. Hellstrand Plasticity of TRPC expression in arterial smooth muscle: correlation with store-operated Ca2+ entry Am J Physiol Cell Physiol, April 1, 2005; 288(4): C872 - C880. [Abstract] [Full Text] [PDF]
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Y. V. Bobkov and B. W. Ache Pharmacological Properties and Functional Role of a TRP-Related Ion Channel in Lobster Olfactory Receptor Neurons J Neurophysiol, March 1, 2005; 93(3): 1372 - 1380. [Abstract] [Full Text] [PDF]
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A. P Albert Activation of TRPC6 channel proteins: evidence for an essential role of phosphorylation J. Physiol., December 1, 2004; 561(2): 354 - 354. [Full Text] [PDF]
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J. Shi, E. Mori, Y. Mori, M. Mori, J. Li, Y. Ito, and R. Inoue Multiple regulation by calcium of murine homologues of transient receptor potential proteins TRPC6 and TRPC7 expressed in HEK293 cells J. Physiol., December 1, 2004; 561(2): 415 - 432. [Abstract] [Full Text] [PDF]
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J.-P. Lievremont, G. St. J. Bird, and J. W. Putney Jr. Canonical transient receptor potential TRPC7 can function as both a receptor- and store-operated channel in HEK-293 cells Am J Physiol Cell Physiol, December 1, 2004; 287(6): C1709 - C1716. [Abstract] [Full Text] [PDF]
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 N. Kunichika, J. W. Landsberg, Y. Yu, H. Kunichika, P. A. Thistlethwaite, L. J. Rubin, and J. X.-J. Yuan Bosentan Inhibits Transient Receptor Potential Channel Expression in Pulmonary Vascular Myocytes Am. J. Respir. Crit. Care Med., November 15, 2004; 170(10): 1101 - 1107. [Abstract] [Full Text] [PDF]
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N. Kunichika, Y. Yu, C. V. Remillard, O. Platoshyn, S. Zhang, and J. X.-J. Yuan Overexpression of TRPC1 enhances pulmonary vasoconstriction induced by capacitative Ca2+ entry Am J Physiol Lung Cell Mol Physiol, November 1, 2004; 287(5): L962 - L969. [Abstract] [Full Text] [PDF]
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A. P Albert and W. A Large Inhibitory regulation of constitutive transient receptor potential-like cation channels in rabbit ear artery myocytes J. Physiol., October 1, 2004; 560(1): 169 - 180. [Abstract] [Full Text] [PDF]
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Y. Yu, I. Fantozzi, C. V. Remillard, J. W. Landsberg, N. Kunichika, O. Platoshyn, D. D. Tigno, P. A. Thistlethwaite, L. J. Rubin, and J. X.-J. Yuan Enhanced expression of transient receptor potential channels in idiopathic pulmonary arterial hypertension PNAS, September 21, 2004; 101(38): 13861 - 13866. [Abstract] [Full Text] [PDF]
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D. J. Beech, K. Muraki, and R. Flemming Non-selective cationic channels of smooth muscle and the mammalian homologues of Drosophila TRP J. Physiol., September 15, 2004; 559(3): 685 - 706. [Abstract] [Full Text] [PDF]
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Y. Takai, R. Sugawara, H. Ohinata, and A. Takai Two types of non-selective cation channel opened by muscarinic stimulation with carbachol in bovine ciliary muscle cells J. Physiol., September 15, 2004; 559(3): 899 - 922. [Abstract] [Full Text] [PDF]
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M.-J. Lin, G. P.H. Leung, W.-M. Zhang, X.-R. Yang, K.-P. Yip, C.-M. Tse, and J. S.K. Sham Chronic Hypoxia-Induced Upregulation of Store-Operated and Receptor-Operated Ca2+ Channels in Pulmonary Arterial Smooth Muscle Cells: A Novel Mechanism of Hypoxic Pulmonary Hypertension Circ. Res., September 3, 2004; 95(5): 496 - 505. [Abstract] [Full Text] [PDF]
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T. Gudermann, M. Mederos y Schnitzler, and A. Dietrich Receptor-Operated Cation Entry--More Than Esoteric Terminology? Sci. Signal., July 27, 2004; 2004(243): pe35 - pe35. [Abstract] [Full Text] [PDF]
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 C. A. Glass and D. O. Bates The role of endothelial cell Ca2+ store release in the regulation of microvascular permeability in vivo Exp Physiol, July 1, 2004; 89(4): 343 - 351. [Abstract] [Full Text] [PDF]
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M. Estacion, S. Li, W. G. Sinkins, M. Gosling, P. Bahra, C. Poll, J. Westwick, and W. P. Schilling Activation of Human TRPC6 Channels by Receptor Stimulation J. Biol. Chem., May 21, 2004; 279(21): 22047 - 22056. [Abstract] [Full Text] [PDF]
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B. Ay, Y. S. Prakash, C. M. Pabelick, and G. C. Sieck Store-operated Ca2+ entry in porcine airway smooth muscle Am J Physiol Lung Cell Mol Physiol, May 1, 2004; 286(5): L909 - L917. [Abstract] [Full Text] [PDF]
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C. Hisatsune, Y. Kuroda, K. Nakamura, T. Inoue, T. Nakamura, T. Michikawa, A. Mizutani, and K. Mikoshiba Regulation of TRPC6 Channel Activity by Tyrosine Phosphorylation J. Biol. Chem., April 30, 2004; 279(18): 18887 - 18894. [Abstract] [Full Text] [PDF]
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 J. W. Landsberg and J. X.-J. Yuan Calcium and TRP Channels in Pulmonary Vascular Smooth Muscle Cell Proliferation Physiology, April 1, 2004; 19(2): 44 - 50. [Abstract] [Full Text] [PDF]
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M. Konrad, K. P. Schlingmann, and T. Gudermann Insights into the molecular nature of magnesium homeostasis Am J Physiol Renal Physiol, April 1, 2004; 286(4): F599 - F605. [Abstract] [Full Text] [PDF]
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J. Wang, L. A. Shimoda, and J. T. Sylvester Capacitative calcium entry and TRPC channel proteins are expressed in rat distal pulmonary arterial smooth muscle Am J Physiol Lung Cell Mol Physiol, April 1, 2004; 286(4): L848 - L858. [Abstract] [Full Text] [PDF]
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