HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) All Versions of this Article: 297/5/C1082    most recent ajpcell.00204.2009v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Google Scholar Articles by Itoh, Y. Articles by Muraki, K. PubMed PubMed Citation Articles by Itoh, Y. Articles by Muraki, K.

Membrane Transporters, Ion Channels, and Pumps

An environmental sensor, TRPV4 is a novel regulator of intracellular Ca²⁺ in human synoviocytes

¹Laboratory of Cellular Pharmacology, School of Pharmacy, Aichi-Gakuin University, Nagoya, Japan; ²Department of Drug Metabolism and Disposition, Graduate School of Pharmaceutical Sciences, Nagoya City University, Nagoya, Japan; ³Department of Molecular Health Sciences, Graduate School of Pharmaceutical Sciences, Nagoya City University, Nagoya, Japan; and ⁴Central Research Laboratories, Kissei Pharmaceutical, Nagano, Japan

Submitted 8 May 2009 ; accepted in final form 11 September 2009

The activation of a vanilloid type 4 transient receptor potential channel (TRPV4) has an obligatory role in regulation of intracellular Ca²⁺ (Ca²⁺_i) in several types of cells including vascular and sensory organs. In this study, we provide evidence that TRPV4 is a functional regulator of Ca²⁺_i in human synoviocytes. Although significant expression of TRPV4 in synoviocytes from patients with (RA) and without (CTR) rheumatoid arthritis was detected at mRNA and protein level, those in the human fibroblast-like synoviocyte line MH7A were rather lower. Consistently, the selective TRPV4 agonist 4-phorbol 12,13-didecanoate (4PDD) effectively elevated Ca²⁺_i in the RA and CTR cells, which was abolished by the removal of external Ca²⁺. Moreover, the elevation was inhibited by ruthenium red, a blocker of TRPVs. In MH7A cells transfected with human TRPV4 (MH7A-V4), 4PDD elevated the Ca²⁺_i in a similar manner to those in the RA and CTR cells. Electrophysiological analysis also revealed that 4PDD activated nonselective cationic currents in RA cells. Application of 227 mosM solution to the RA and MH7A-V4 cells elevated their Ca²⁺_i, but this does not occur when it was applied to MH7A cells. Treatment of RA but not MH7A cells with 4PDD for 24 h reduced their production of IL-8. These results suggest that an environmental sensor, TRPV4, is a novel regulator of intracellular Ca²⁺ in human synoviocytes.

MH7A; rheumatoid arthritis; vanilloid type 4 transient receptor potential channel; 4-phorbol 12,13-didecanoate; Ca²⁺ concentration; hypotonic stimulation; interleukin-8