© 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
This article has been cited by other articles:
 |
|
 |
|
  R. Berra-Romani, A. Mazzocco-Spezzia, M. V. Pulina, and V. A. Golovina Ca2+ handling is altered when arterial myocytes progress from a contractile to a proliferative phenotype in culture Am J Physiol Cell Physiol, September 1, 2008; 295(3): C779 - C790. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Takahashi, H. Lin, N. Geshi, Y. Mori, Y. Kawarabayashi, N. Takami, M. X. Mori, A. Honda, and R. Inoue Nitric oxide-cGMP-protein kinase G pathway negatively regulates vascular transient receptor potential channel TRPC6 J. Physiol., September 1, 2008; 586(17): 4209 - 4223. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Alvarez, A. Coulombe, O. Cazorla, M. Ugur, J.-M. Rauzier, J. Magyar, E.-L. Mathieu, G. Boulay, R. Souto, P. Bideaux, et al. ATP/UTP activate cation-permeable channels with TRPC3/7 properties in rat cardiomyocytes Am J Physiol Heart Circ Physiol, July 1, 2008; 295(1): H21 - H28. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. P. Albert, S. N. Saleh, and W. A. Large Inhibition of native TRPC6 channel activity by phosphatidylinositol 4,5-bisphosphate in mesenteric artery myocytes J. Physiol., July 1, 2008; 586(13): 3087 - 3095. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
I. N. Bratz, G. M. Dick, J. D. Tune, J. M. Edwards, Z. P. Neeb, U. D. Dincer, and M. Sturek Impaired capsaicin-induced relaxation of coronary arteries in a porcine model of the metabolic syndrome Am J Physiol Heart Circ Physiol, June 1, 2008; 294(6): H2489 - H2496. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. N. Saleh, A. P. Albert, C. M. Peppiatt-Wildman, and W. A. Large Diverse properties of store-operated TRPC channels activated by protein kinase C in vascular myocytes J. Physiol., May 15, 2008; 586(10): 2463 - 2476. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Alvina and K. Khodakhah Selective regulation of spontaneous activity of neurons of the deep cerebellar nuclei by N-type calcium channels in juvenile rats J. Physiol., May 15, 2008; 586(10): 2523 - 2538. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Zhang, T. A. Roepke, M. J. Kelly, and O. K. Ronnekleiv Kisspeptin Depolarizes Gonadotropin-Releasing Hormone Neurons through Activation of TRPC-Like Cationic Channels J. Neurosci., April 23, 2008; 28(17): 4423 - 4434. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. Villalba, E. Stankevicius, U. Simonsen, and D. Prieto Rho kinase is involved in Ca2+ entry of rat penile small arteries Am J Physiol Heart Circ Physiol, April 1, 2008; 294(4): H1923 - H1932. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. K. Fellner and W. J. Arendshorst Angiotensin II-stimulated Ca2+ entry mechanisms in afferent arterioles: role of transient receptor potential canonical channels and reverse Na+/Ca2+ exchange Am J Physiol Renal Physiol, January 1, 2008; 294(1): F212 - F219. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y. Maruyama, T. Ogura, K. Mio, S. Kiyonaka, K. Kato, Y. Mori, and C. Sato Three-dimensional Reconstruction Using Transmission Electron Microscopy Reveals a Swollen, Bell-shaped Structure of Transient Receptor Potential Melastatin Type 2 Cation Channel J. Biol. Chem., December 21, 2007; 282(51): 36961 - 36970. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. T. E. Hartwick, J. R. Bramley, J. Yu, K. T. Stevens, C. N. Allen, W. H. Baldridge, P. J. Sollars, and G. E. Pickard Light-Evoked Calcium Responses of Isolated Melanopsin-Expressing Retinal Ganglion Cells J. Neurosci., December 5, 2007; 27(49): 13468 - 13480. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. Poburko, C.-H. Liao, V. S. Lemos, E. Lin, Y. Maruyama, W. C. Cole, and C. van Breemen Transient Receptor Potential Channel 6 Mediated, Localized Cytosolic [Na+] Transients Drive Na+/Ca2+ Exchanger Mediated Ca2+ Entry in Purinergically Stimulated Aorta Smooth Muscle Cells Circ. Res., November 9, 2007; 101(10): 1030 - 1038. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. Teruyama and W. E. Armstrong Calcium-Dependent Fast Depolarizing Afterpotentials in Vasopressin Neurons in the Rat Supraoptic Nucleus J Neurophysiol, November 1, 2007; 98(5): 2612 - 2621. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. J. Sandoval, J. P. Riquelme, M. D. Carretta, J. L. Hancke, M. A. Hidalgo, and R. A. Burgos Store-operated calcium entry mediates intracellular alkalinization, ERK1/2, and Akt/PKB phosphorylation in bovine neutrophils J. Leukoc. Biol., November 1, 2007; 82(5): 1266 - 1277. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Goel, W. G. Sinkins, C.-D. Zuo, U. Hopfer, and W. P. Schilling Vasopressin-induced membrane trafficking of TRPC3 and AQP2 channels in cells of the rat renal collecting duct Am J Physiol Renal Physiol, November 1, 2007; 293(5): F1476 - F1488. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
F. Suzuki, S. Morishima, T. Tanaka, and I. Muramatsu Snapin, a New Regulator of Receptor Signaling, Augments {alpha}1A-Adrenoceptor-operated Calcium Influx through TRPC6 J. Biol. Chem., October 5, 2007; 282(40): 29563 - 29573. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. I. Clyman, N. Waleh, H. Kajino, C. Roman, and F. Mauray Calcium-dependent and calcium-sensitizing pathways in the mature and immature ductus arteriosus Am J Physiol Regulatory Integrative Comp Physiol, October 1, 2007; 293(4): R1650 - R1656. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Graham, M. Ding, S. Sours-Brothers, T. Yorio, J.-X. Ma, and R. Ma Downregulation of TRPC6 protein expression by high glucose, a possible mechanism for the impaired Ca2+ signaling in glomerular mesangial cells in diabetes Am J Physiol Renal Physiol, October 1, 2007; 293(4): F1381 - F1390. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. P. Berg, N. Sen, and D. A. Bayliss TrpC3/C7 and Slo2.1 Are Molecular Targets for Metabotropic Glutamate Receptor Signaling in Rat Striatal Cholinergic Interneurons J. Neurosci., August 15, 2007; 27(33): 8845 - 8856. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. P. Albert, S. N. Saleh, C. M. Peppiatt-Wildman, and W. A. Large Multiple activation mechanisms of store-operated TRPC channels in smooth muscle cells J. Physiol., August 15, 2007; 583(1): 25 - 36. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. A. Reading and J. E. Brayden Central Role of TRPM4 Channels in Cerebral Blood Flow Regulation Stroke, August 1, 2007; 38(8): 2322 - 2328. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. A. Hill and M. J. Davis Coupling a change in intraluminal pressure to vascular smooth muscle depolarization: still stretching for an explanation Am J Physiol Heart Circ Physiol, June 1, 2007; 292(6): H2570 - H2572. [Full Text] [PDF]
|
|
|
|
|
|
A. Malkia, R. Madrid, V. Meseguer, E. de la Pena, M. Valero, C. Belmonte, and F. Viana Bidirectional shifts of TRPM8 channel gating by temperature and chemical agents modulate the cold sensitivity of mammalian thermoreceptors J. Physiol., May 15, 2007; 581(1): 155 - 174. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
F. A. Ene, A. Kalmbach, and K. Kandler Metabotropic Glutamate Receptors in the Lateral Superior Olive Activate TRP-Like Channels: Age- and Experience-Dependent Regulation J Neurophysiol, May 1, 2007; 97(5): 3365 - 3375. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. M. Peppiatt-Wildman, A. P. Albert, S. N. Saleh, and W. A. Large Endothelin-1 activates a Ca2+-permeable cation channel with TRPC3 and TRPC7 properties in rabbit coronary artery myocytes J. Physiol., May 1, 2007; 580(3): 755 - 764. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Kosugi, T. Nakatsuka, T. Fujita, Y. Kuroda, and E. Kumamoto Activation of TRPA1 Channel Facilitates Excitatory Synaptic Transmission in Substantia Gelatinosa Neurons of the Adult Rat Spinal Cord J. Neurosci., April 18, 2007; 27(16): 4443 - 4451. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Sekaran, G. S. Lall, K. L. Ralphs, A. J. Wolstenholme, R. J. Lucas, R. G. Foster, and M. W. Hankins 2-Aminoethoxydiphenylborane Is an Acute Inhibitor of Directly Photosensitive Retinal Ganglion Cell Activity In Vitro and In Vivo J. Neurosci., April 11, 2007; 27(15): 3981 - 3986. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Tosun, Y. Erac, C. Selli, and N. Karakaya Sarcoplasmic-endoplasmic reticulum Ca2+-ATPase inhibition prevents endothelin A receptor antagonism in rat aorta Am J Physiol Heart Circ Physiol, April 1, 2007; 292(4): H1961 - H1966. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y. Bobkov and B. Ache Block by Amiloride Derivatives of Odor-Evoked Discharge in Lobster Olfactory Receptor Neurons through Action on a Presumptive TRP Channel Chem Senses, February 1, 2007; 32(2): 149 - 159. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. C. Hardie TRP channels and lipids: from Drosophila to mammalian physiology J. Physiol., January 1, 2007; 578(1): 9 - 24. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. Weissmann, A. Dietrich, B. Fuchs, H. Kalwa, M. Ay, R. Dumitrascu, A. Olschewski, U. Storch, M. Mederos y Schnitzler, H. A. Ghofrani, et al. Classical transient receptor potential channel 6 (TRPC6) is essential for hypoxic pulmonary vasoconstriction and alveolar gas exchange PNAS, December 12, 2006; 103(50): 19093 - 19098. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. N. Saleh, A. P. Albert, C. M. Peppiatt, and W. A. Large Angiotensin II activates two cation conductances with distinct TRPC1 and TRPC6 channel properties in rabbit mesenteric artery myocytes J. Physiol., December 1, 2006; 577(2): 479 - 495. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S.-Z. Xu, G. Boulay, R. Flemming, and D. J. Beech E3-targeted anti-TRPC5 antibody inhibits store-operated calcium entry in freshly isolated pial arterioles Am J Physiol Heart Circ Physiol, December 1, 2006; 291(6): H2653 - H2659. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
W. F. Jackson Vascular smooth muscle store-operated Ca2+ channels: what a TRP! Am J Physiol Heart Circ Physiol, December 1, 2006; 291(6): H2592 - H2594. [Full Text] [PDF]
|
|
|
|
|
|
R. N. Carter, G. Tolhurst, G. Walmsley, M. Vizuete-Forster, N. Miller, and M. P. Mahaut-Smith Molecular and electrophysiological characterization of transient receptor potential ion channels in the primary murine megakaryocyte J. Physiol., October 1, 2006; 576(1): 151 - 162. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H.-W. Cheng, A.F. James, R.R. Foster, J.C. Hancox, and D.O. Bates VEGF Activates Receptor-Operated Cation Channels in Human Microvascular Endothelial Cells Arterioscler. Thromb. Vasc. Biol., August 1, 2006; 26(8): 1768 - 1776. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Inoue, L. J. Jensen, J. Shi, H. Morita, M. Nishida, A. Honda, and Y. Ito Transient Receptor Potential Channels in Cardiovascular Function and Disease Circ. Res., July 21, 2006; 99(2): 119 - 131. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Earley Molecular Diversity of Receptor Operated Channels in Vascular Smooth Muscle: A Role for Heteromultimeric TRP Channels? Circ. Res., June 23, 2006; 98(12): 1462 - 1464. [Full Text] [PDF]
|
|
|
|
|
|
Y. Maruyama, Y. Nakanishi, E. J. Walsh, D. P. Wilson, D. G. Welsh, and W. C. Cole Heteromultimeric TRPC6-TRPC7 Channels Contribute to Arginine Vasopressin-Induced Cation Current of A7r5 Vascular Smooth Muscle Cells Circ. Res., June 23, 2006; 98(12): 1520 - 1527. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S.-Z. Xu, K. Muraki, F. Zeng, J. Li, P. Sukumar, S. Shah, A. M. Dedman, P. K. Flemming, D. McHugh, J. Naylor, et al. A Sphingosine-1-Phosphate-Activated Calcium Channel Controlling Vascular Smooth Muscle Cell Motility Circ. Res., June 9, 2006; 98(11): 1381 - 1389. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 X.-R. Yang, M.-J. Lin, L. S. McIntosh, and J. S. K. Sham Functional expression of transient receptor potential melastatin- and vanilloid-related channels in pulmonary arterial and aortic smooth muscle Am J Physiol Lung Cell Mol Physiol, June 1, 2006; 290(6): L1267 - L1276. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Sours, J. Du, S. Chu, M. Ding, X. J. Zhou, and R. Ma Expression of canonical transient receptor potential (TRPC) proteins in human glomerular mesangial cells Am J Physiol Renal Physiol, June 1, 2006; 290(6): F1507 - F1515. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. I. Brueggemann, D. R. Markun, K. K. Henderson, L. L. Cribbs, and K. L. Byron Pharmacological and Electrophysiological Characterization of Store-Operated Currents and Capacitative Ca2+ Entry in Vascular Smooth Muscle Cells J. Pharmacol. Exp. Ther., May 1, 2006; 317(2): 488 - 499. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. T. Smyth, L. Lemonnier, G. Vazquez, G. S. Bird, and J. W. Putney Jr. Dissociation of Regulated Trafficking of TRPC3 Channels to the Plasma Membrane from Their Activation by Phospholipase C J. Biol. Chem., April 28, 2006; 281(17): 11712 - 11720. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Estacion, W. G. Sinkins, S. W. Jones, M. A. B. Applegate, and W. P. Schilling Human TRPC6 expressed in HEK 293 cells forms non-selective cation channels with limited Ca2+ permeability J. Physiol., April 15, 2006; 572(2): 359 - 377. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. T. Kim, B. J. Kim, J. H. Lee, S. C. Kwon, D. S. Yeon, D. K. Yang, I. So, and K. W. Kim Involvement of calmodulin and myosin light chain kinase in activation of mTRPC5 expressed in HEK cells Am J Physiol Cell Physiol, April 1, 2006; 290(4): C1031 - C1040. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. O. Hernandez-Gonzalez, J. Sosnik, J. Edwards, J. J. Acevedo, I. Mendoza-Lujambio, I. Lopez-Gonzalez, I. Demarco, E. Wertheimer, A. Darszon, and P. E. Visconti Sodium and Epithelial Sodium Channels Participate in the Regulation of the Capacitation-associated Hyperpolarization in Mouse Sperm J. Biol. Chem., March 3, 2006; 281(9): 5623 - 5633. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. P. Albert, V. Pucovsky, S. A. Prestwich, and W. A. Large TRPC3 properties of a native constitutively active Ca2+-permeable cation channel in rabbit ear artery myocytes J. Physiol., March 1, 2006; 571(2): 361 - 369. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Thebault, M. Flourakis, K. Vanoverberghe, F. Vandermoere, M. Roudbaraki, V. Lehen'kyi, C. Slomianny, B. Beck, P. Mariot, J.-L. Bonnal, et al. Differential Role of Transient Receptor Potential Channels in Ca2+ Entry and Proliferation of Prostate Cancer Epithelial Cells Cancer Res., February 15, 2006; 66(4): 2038 - 2047. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
V. A. Snetkov, G. A Knock, L. Baxter, G. D. Thomas, J. P. T. Ward, and P. I. Aaronson Mechanisms of the prostaglandin F2{alpha}-induced rise in [Ca2+]i in rat intrapulmonary arteries J. Physiol., February 15, 2006; 571(1): 147 - 163. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. Ma, J. Du, S. Sours, and M. Ding Store-Operated Ca2+ Channel in Renal Microcirculation and Glomeruli Experimental Biology and Medicine, February 1, 2006; 231(2): 145 - 153. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. Pelucchi, G. Aguiari, A. Pignatelli, E. Manzati, R. Witzgall, L. del Senno, and O. Belluzzi Nonspecific Cation Current Associated with Native Polycystin-2 in HEK-293 Cells J. Am. Soc. Nephrol., February 1, 2006; 17(2): 388 - 397. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. P. Albert and W. A. Large Signal transduction pathways and gating mechanisms of native TRP-like cation channels in vascular myocytes J. Physiol., January 1, 2006; 570(1): 45 - 51. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Soboloff, M. Spassova, W. Xu, L.-P. He, N. Cuesta, and D. L. Gill Role of Endogenous TRPC6 Channels in Ca2+ Signal Generation in A7r5 Smooth Muscle Cells J. Biol. Chem., December 2, 2005; 280(48): 39786 - 39794. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 |