The contribution of endogenous and recombinant transient receptor potential vanilloid type 6 (TRPV6) channels to Ca[sup 2+] entry across the plasma membrane was studied in the human lymph node prostate cancer cell line (LNCaP). LNCaP cells do express the TRPV6 gene, and Ca[sup 2+] entry currents in these cells were detected after active and passive Ca[sup 2+] store depletion by intracellular application of inositol 1,4,5-trisphosphate, Ca[sup 2+] chelators, and the sarcoplasmic/endoplasmic reticulum Ca[sup 2+]ATPase inhibitor thapsigargin. This store-operated Ca[sup 2+] current (I[sub SOC]) had biophysical properties similar to those of the Ca[sup 2+] release-activated Ca[sup 2+] current (I[sub CRAC]) in rat basophilic leukemia cells such as the activation mechanism, inward rectification, and Ca[sup 2+] selectivity. These properties are also shared by the Ca[sup 2+]-sensing Ca[sup 2+] current (I[sub TRPV6]) recorded after heterologous expression of TRPV6 cDNA in human embryonic kidney and rat basophilic leukemia cells (Bödding, M., Wissenbach, U., Flockerzi, V. (2002) J. Biol. Chem. 277, 36656-36664). TRPV6 cDNA transfection of LNCaP cells restored recombinant I[sub TRPV6], which can be distinguished from I[sub SOC] by the mechanism of activation, the voltage dependence of monovalent currents in the absence of external divalent cations, and the changes in Ca[sup 2+] current densities due to different membrane potentials. In addition, I[sub SOC] was not affected by antiandrogen or 1,25-dihydroxyvitamin D[sub 3] treatment of LNCaP cells, which up-regulates TRPV6 gene expression, or by androgen treatment, which has the opposite effect. Therefore, native channels responsible for I[sub SOC] are different from those for recombinant I[sub TRPV6] and do not appear to be affected if one of their assumed subunits, TRPV6, is up- or down-regulated, suggesting a rather rigid subunit composition in vivo. [ABSTRACT FROM AUTHOR]