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J. Biol. Chem., Vol. 278, Issue 25, 22664-22668, June 20, 2003
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¶
From the
Department of Pharmacology, Jichi Medical School, 3311-1 Yakushiji, Minamikawachi, Tochigi 329-0498, Japan and the Pharmaceutical Technology Laboratory, Chugai Pharmaceutical Co., Ltd., Shizuoka 412-8513, Japan
The sensation of pressure, mechanosensation, in vertebrates remains poorly understood on the molecular level. The ion channel TRPV4 is in the TRP family and is a candidate for a mechanosensitive calcium-permeable channel. It is located in dorsal root ganglia. In the present study, we show that disrupting the Trpv4 gene in mice markedly reduced the sensitivity of the tail to pressure and acidic nociception. The threshold to noxious stimuli and the conduction velocity of myelinated nerve responding to stimuli were also impaired. Activation of unmyelinated nerve was undetected. However, the mouse still retained olfaction, taste sensation, and heat avoidance. The TRPV4 channel expressed in vitro in Chinese hamster ovary cells was opened by low pH, citrate, and inflation but not by heat or capsaicin. These data identify the TRPV4 channel as essential for the normal detection of pressure and as a receptor of the high-threshold mechanosensory complex.
Received for publication, March 13, 2003 Accepted for publication April 5, 2003.
The nucleotide sequence(s) reported in this paper has been submitted to the GenBankTM/EBI Data Bank with accession number(s) AB021875
* This work was supported in part by a grant from the Ministry of Culture, Education, and Science, Japan. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
¶ To whom correspondence should be addressed. Tel.: 81-285-58-7326; Fax: 81-285-44-5541; E-mail: macsuz{at}jichi.ac.jp.
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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]
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