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This Article Full Text Full Text (PDF) Corrigendum All Versions of this Article: 294/4/F909    most recent 00606.2007v1 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 ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Google Scholar Articles by Du, J. Articles by Ma, R. PubMed PubMed Citation Articles by Du, J. Articles by Ma, R.

Mediation of angiotensin II-induced Ca²⁺ signaling by polycystin 2 in glomerular mesangial cells

¹Department of Integrative Physiology, University of North Texas Health Science Center at Fort Worth, Fort Worth, Texas; and ²Department of Physiology, Anhui Medical University, Hefei, Peoples Republic of China

Submitted 20 December 2007 ; accepted in final form 31 January 2008

Ca⁺ influx across the plasma membrane is a major component of mesangial cell (MC) response to vasoconstrictors. Polycystin 2 (PC2), the protein product of the gene mutated in type 2 autosomal dominant polycystic kidney disease, has been shown to function as a nonselective cation channel in a variety of cell types. The present study was performed to test the hypothesis that PC2 and its binding partners constitute a Ca²⁺-permeable channel and contribute to ANG II-induced Ca²⁺ signaling in MCs. Western blot and immunocytochemistry showed PC2 expression in cultured human MCs. The existence of PC2 in MCs was further confirmed by immunohistochemsitry in rat kidney sections. Coimmunoprecipitation displayed a selective interaction of PC2 with canonical transient receptor potential (TRPC) proteins TRPC1 and TRPC4. Cell-attached patch-clamp experiments revealed that ANG II-induced membrane currents were enhanced by overexpression of pkd2 but significantly inhibited by knock down of pkd2, 30 µM Gd³⁺ (a PC2 channel blocker), and dominant-negative pkd2 mutant (pkd2-D511V). Corresponding to the increase in channel currents, ANG II stimulation increased expression of PC2 on the cell surface of MCs and interaction with TRPC1 and TRPC4. Furthermore, ANG II-induced MC contraction was significantly reduced in pkd2-knocked down MCs. These data suggest that PC2 selectively assembles with TRPC1 and TRPC4 to form channel complexes mediating ANG II-induced Ca²⁺ responses in MCs.

calcium channel