1. ¹Medizinische Klinik IV, Charité Campus Benjamin Franklin, Berlin, Germany
2. ²Department of Hypertension and Endocrinology, Daping Hospital, Third Military Medical University, Chongqing, PR China
3. ³Institut für Klinische Pharmakologie und Toxikologie, Charité Campus Benjamin Franklin, Berlin, Germany

Correspondence: Dr. Martin Tepel, Med. Klinik IV, Nephrologie Department of Hypertension and Endocrinology, Charité Campus Benjamin Franklin, Hindenburgdamm 30, D-12200 Berlin, Germany E-mail: Martin.Tepel@charite.de

Received 22 January 2005; Revised 18 March 2005; Accepted 12 May 2005.

Abstract

Background: Disturbances in the regulation of cytosolic calcium concentration have been attributed to primary hypertension, but the role of calcium-permeable transient receptor potential canonical channel 3 (TRPC3) has not yet been evaluated in primary hypertension.

Methods: Expression of TRPC3 was determined using in-cell Western assay. Evaluation of RNA interference for the downregulation of a specific gene in cells by small interfering RNA was performed. Measurements of cytosolic calcium were carried out using the fluorescent dye fura2.

Results: Expression of TRPC3 was significantly increased in monocytes from spontaneously hypertensive rats (SHR) compared with normotensive Wistar-Kyoto rats (WKY). Transplasmamembrane calcium influx and thapsigargin-induced sustained calcium increase were significantly higher in SHR compared with WKY. In the presence of the TRP channel blocker SKF-96365 these differences were no longer observed. Specific TRPC3-knockdown by transfection of monocytes from SHR with small interfering RNA significantly reduced TRPC3 expression, trans–plasma membrane calcium influx, and thapsigargin-induced sustained calcium increase.

Conclusions: This study shows, for the first time, increased TRPC3 channel expression and increased TRPC3-related calcium influx in SHR.