Ca2+ influx through plasma membrane is a major component of MC response to vasoconstrictors. PKD2, the protein product of the gene mutated in type 2 autosomal dominant polycystic kidney disease, has been shown to function as an non-selective cation channel (NSCC) in renal tubular epithelial cells. The present study was performed to test the hypothesis that PKD2 and its binding partner constitute NSCC in MCs and contribute to contractile function of the cells. Western blotting and immunocytochemistry showed PKD2 expression in cultured human MCs. The existence of PKD2 in MCs was further confirmed by immunohistochemsitry in rat and human kidney sections. Co-immunoprecipitation showed a selective interaction of PKD2 with TRPC1 and TRPC4. Cell-attached patch clamp experiments revealed nonselective cationic currents stimulated by Ang II. The Agonist-induced currents were enhanced by over-expressing PKD2, but attenuated by knocking down PKD2. Corresponding to the increase in channel currents, Ang II stimulation increased expression of PKD2 in the cell surface as well as interaction with TRPC4. Furthermore, Ang II-induced MC contraction was reduced in PKD2 knocked out MCs. These data suggest that PKD2 might selectively assemble with specific isoform of TRPC proteins to form NSCC in MCs and this channel complex contributes to contractile function of MCs. (supported by AHA SDG)