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Previous Article | Next Article
The Journal of Neuroscience, August 1, 2002, 22(15):6408-6414
Heat-Evoked Activation of the Ion Channel, TRPV4
Ali Deniz Güler1, Hyosang Lee1, Tohko Iida2, Isao Shimizu1, 3, Makoto Tominaga2, and Michael Caterina1 1 Departments of Biological Chemistry and Neuroscience, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, 2 Department of Physiology, Mie University School of Medicine, Tsu/Mie 514-8507, Japan, and 3 Dainippon Pharmaceutical Company, Limited, Suita/Osaka 564-0053, Japan
The mammalian nervous system constantly evaluates internal and environmental temperatures to maintain homeostasis and to avoid thermal extremes. Several members of the transient receptor potential (TRP) family of ion channels have been implicated as transducers of thermal stimuli, including TRPV1 and TRPV2, which are activated by heat, and TRPM8, which is activated by cold. Here we demonstrate that another member of the TRP family, TRPV4, previously described as a hypo-osmolarity-activated ion channel, also can be activated by heat. In response to warm temperatures, TRPV4 mediates large inward currents in Xenopus oocytes and both inward currents and calcium influx into human embryonic kidney 293 cells. In both cases these responses are observed at temperatures lower than those required to activate TRPV1 and can be inhibited reversibly by ruthenium red. Heat-evoked TRPV4-mediated responses are greater in hypo-osmotic solutions and reduced in hyperosmotic solutions. Consistent with these functional properties, we observed TRPV4 immunoreactivity in anterior hypothalamic structures involved in temperature sensation and the integration of thermal and osmotic information. Together, these data implicate TRPV4 as a possible transducer of warm stimuli within the hypothalamus.
Key words: TRPV4; OTRPC4; VR-OAC; VRL-2; TRP12; heat; ion channel; thermotransduction; osmolarity; hypothalamus
Copyright © 2002 Society for Neuroscience 0270-6474/02/22156408-07$05.00/0
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Motoneurons Express Heteromeric TWIK-Related Acid-Sensitive K+ (TASK) Channels Containing TASK-1 (KCNK3) and TASK-3 (KCNK9) Subunits
J. Neurosci., July 28, 2004; 24(30): 6693 - 6702.
[Abstract] [Full Text] [PDF]
A. J. Stokes, L. M.N. Shimoda, M. Koblan-Huberson, C. N. Adra, and H. Turner
A TRPV2-PKA Signaling Module for Transduction of Physical Stimuli in Mast Cells
J. Exp. Med., July 19, 2004; 200(2): 137 - 147.
[Abstract] [Full Text] [PDF]
C. J. Woodbury, M. Zwick, S. Wang, J. J. Lawson, M. J. Caterina, M. Koltzenburg, K. M. Albers, H. R. Koerber, and B. M. Davis
Nociceptors Lacking TRPV1 and TRPV2 Have Normal Heat Responses
J. Neurosci., July 14, 2004; 24(28): 6410 - 6415.
[Abstract] [Full Text] [PDF]
C.-L. Huang
The Transient Receptor Potential Superfamily of Ion Channels
J. Am. Soc. Nephrol., July 1, 2004; 15(7): 1690 - 1699.
[Abstract] [Full Text] [PDF]
W. Tian, M. Salanova, H. Xu, J. N. Lindsley, T. T. Oyama, S. Anderson, S. Bachmann, and D. M. Cohen
Renal expression of osmotically responsive cation channel TRPV4 is restricted to water-impermeant nephron segments
Am J Physiol Renal Physiol, July 1, 2004; 287(1): F17 - F24.
[Abstract] [Full Text] [PDF]
M.-K. Chung, H. Lee, A. Mizuno, M. Suzuki, and M. J. Caterina
2-Aminoethoxydiphenyl Borate Activates and Sensitizes the Heat-Gated Ion Channel TRPV3
J. Neurosci., June 2, 2004; 24(22): 5177 - 5182.
[Abstract] [Full Text] [PDF]
L. Zhang, S. Jones, K. Brody, M. Costa, and S. J. H. Brookes
Thermosensitive transient receptor potential channels in vagal afferent neurons of the mouse
Am J Physiol Gastrointest Liver Physiol, June 1, 2004; 286(6): G983 - G991.
[Abstract] [Full Text] [PDF]
M.-K. Chung, H. Lee, A. Mizuno, M. Suzuki, and M. J. Caterina
TRPV3 and TRPV4 Mediate Warmth-evoked Currents in Primary Mouse Keratinocytes
J. Biol. Chem., May 14, 2004; 279(20): 21569 - 21575.
[Abstract] [Full Text] [PDF]
N. Alessandri-Haber, O. A. Dina, J. J. Yeh, C. A. Parada, D. B. Reichling, and J. D. Levine
Transient Receptor Potential Vanilloid 4 Is Essential in Chemotherapy-Induced Neuropathic Pain in the Rat
J. Neurosci., May 5, 2004; 24(18): 4444 - 4452.
[Abstract] [Full Text] [PDF]
B. Nilius, J. Vriens, J. Prenen, G. Droogmans, and T. Voets
TRPV4 calcium entry channel: a paradigm for gating diversity
Am J Physiol Cell Physiol, February 1, 2004; 286(2): C195 - C205.
[Abstract] [Full Text] [PDF]
J. Vriens, H. Watanabe, A. Janssens, G. Droogmans, T. Voets, and B. Nilius
Cell swelling, heat, and chemical agonists use distinct pathways for the activation of the cation channel TRPV4
PNAS, January 6, 2004; 101(1): 396 - 401.
[Abstract] [Full Text] [PDF]
R. G. O'Neil and R. C. Brown
The Vanilloid Receptor Family of Calcium-Permeable Channels: Molecular Integrators of Microenvironmental Stimuli
Physiology, December 1, 2003; 18(6): 226 - 231.
[Abstract] [Full Text] [PDF]
D. E. Clapham, C. Montell, G. Schultz, and D. Julius
International Union of Pharmacology. XLIII. Compendium of Voltage-Gated Ion Channels: Transient Receptor Potential Channels
Pharmacol. Rev., December 1, 2003; 55(4): 591 - 596.
[Abstract] [Full Text] [PDF]
W. Liedtke, D. M. Tobin, C. I. Bargmann, and J. M. Friedman
Mammalian TRPV4 (VR-OAC) directs behavioral responses to osmotic and mechanical stimuli in Caenorhabditis elegans
PNAS, November 25, 2003; 100(suppl_2): 14531 - 14536.
[Abstract] [Full Text]
W. Liedtke and J. M. Friedman
Abnormal osmotic regulation in trpv4-/- mice
PNAS, November 11, 2003; 100(23): 13698 - 13703.
[Abstract] [Full Text] [PDF]
K. Muraki, Y. Iwata, Y. Katanosaka, T. Ito, S. Ohya, M. Shigekawa, and Y. Imaizumi
TRPV2 Is a Component of Osmotically Sensitive Cation Channels in Murine Aortic Myocytes
Circ. Res., October 31, 2003; 93(9): 829 - 838.
[Abstract] [Full Text] [PDF]
M.-K. Chung, H. Lee, and M. J. Caterina
Warm Temperatures Activate TRPV4 in Mouse 308 Keratinocytes
J. Biol. Chem., August 22, 2003; 278(34): 32037 - 32046.
[Abstract] [Full Text] [PDF]
R. Strotmann, G. Schultz, and T. D. Plant
Ca2+-dependent Potentiation of the Nonselective Cation Channel TRPV4 Is Mediated by a C-terminal Calmodulin Binding Site
J. Biol. Chem., July 11, 2003; 278(29): 26541 - 26549.
[Abstract] [Full Text] [PDF]
X. Gao, L. Wu, and R. G. O'Neil
Temperature-modulated Diversity of TRPV4 Channel Gating: ACTIVATION BY PHYSICAL STRESSES AND PHORBOL ESTER DERIVATIVES THROUGH PROTEIN KINASE C-DEPENDENT AND -INDEPENDENT PATHWAYS
J. Biol. Chem., July 11, 2003; 278(29): 27129 - 27137.
[Abstract] [Full Text] [PDF]
J. Zheng, C. Dai, P. S. Steyger, Y. Kim, Z. Vass, T. Ren, and A. L. Nuttall
Vanilloid Receptors in Hearing: Altered Cochlear Sensitivity by Vanilloids and Expression of TRPV1 in the Organ of Corti
J Neurophysiol, July 1, 2003; 90(1): 444 - 455.
[Abstract] [Full Text] [PDF]
V. Vlachova, J. Teisinger, K. Susankova, A. Lyfenko, R. Ettrich, and L. Vyklicky
Functional Role of C-Terminal Cytoplasmic Tail of Rat Vanilloid Receptor 1
J. Neurosci., February 15, 2003; 23(4): 1340 - 1350.
[Abstract] [Full Text] [PDF]
S. Dirajlal, L. E. Pauers, and C. L. Stucky
Differential Response Properties of IB4-Positive and -Negative Unmyelinated Sensory Neurons to Protons and Capsaicin
J Neurophysiol, January 1, 2003; 89(1): 513 - 524.
[Abstract] [Full Text] [PDF]
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