Epithelial Ca2+ Channel

TRPV5 and TRPV6, also known as the epithelial Ca2+ channel or ECaC (TRPV5) and Ca2+transporter 1 or Ca2+ transporter-like (TRPV6), are the only two Ca2+-selective TRP channels identified so far. They may function in vitamin D-dependent transcellular transport of Ca2+in kidney, intestine and placenta. TRPV6 is also expressed in pancreatic acinar cells, and in prostate cancer, but not in healthy prostate or in benign prostate hyperplasia. 

Nilius B, Vennekens R, Prenen J, Hoenderop JGJ, Droogmans G, Bindels 2001 The single pore residue Asp752 determines Ca2+ permeation and Mg2+ block of the epithelial Ca2+ channel. J Biol Chem 276 1020-1025... 

Epithelial calcium channel 1 (ECaCl), synonym TRJPV5, is a member ofthe TRP family of ion channels, implicated in vitamin D-dependent transcellular Ca2+ transport in epithelial cells ofthe kidney, placenta and the intestine. 

There is growing evidence implicating Na+-dependent solute transporters and intracellular as well as extracellular Ca2+ in the physiological regulation of the paracellular pathway [81,203,204], Such modulation of paracellular permeability is especially important for drugs such as peptides and oligonucleotides that exhibit poor permeability characteristics across both the cornea and the conjunctiva [150,152,154,155], In addition, ion transporters such as Cl and Ca2+ channels have been implicated in macromolecular transport (see Sections IV.B.2 and IV.B.4). In the following discussion, some key ion transport processes and their possible roles in solute transport across epithelial tissues are summarized. 

Because K+ does not recycle across the apical membrane of the DCT as it does in the TAL, there is no lumen-positive potential in this segment, and Ca2+ and Mg2+ are not driven out of the tubular lumen by electrical forces. Instead, Ca2+ is actively reabsorbed by the DCT epithelial cell via an apical Ca2+ channel and basolateral Na+/Ca2+ exchanger (Figure 15-4). This process is regulated by parathyroid hormone. 

Vanden Abeele, F., Lemonnier, L., Thebault, S., Lepage, G., Parys, J. B., Shuba, Y., Skryma, R. and Prevarskaya, N., 2004, Two types of store-operated Ca2+ channels with different activation modes and molecular origin in LNCaP human prostate cancer epithelial cells. J Biol Chem 279,... 

Bacskai BJ, Friedman PA. Activation of latent Ca2+-channels in renal epithelial cells by parathyroid hormone. Nature 1990 347 388-391. 

CaSR may also influence the proliferative and apoptotic status of the cells indirectly via modulation of cell volume homeostasis. Indeed, stimulation of CaSR in human epithelial cells induces upregulation of volume-regulated anion channels (VRAC) via a G protein-mediated increase in intracellular cAMP (Shimizu, et al., 2000). Proliferation and apoptosis are associated with essential volume perturbations [e.g., (Lang, et al., 2000)] and VRAC, a key component of homeostatic volume regulation, has been directly implicated in proliferation (Chen, et al., 2002, Doroshenko, et al., 2001, Shen, et al., 2000, Wang, et al., 2002) and apoptosis (Lemonnier, et al., 2004, Okada, et al., 2001, Okada, et al., 2006, Shen, et al., 2002). Consequently, extracellular Ca2+ may affect carcinogenesis via the CaSR-VRAC-cell volume links. The Ca2+ -permeable store-operated channel (SOC) is directly and functionally coupled to VRAC in an androgen-dependent LNCaP human prostate cancer epithelial cell line (Lemonnier, et al., 2002), evidence for another, CaSR-unrelated, potential mechanism for extracellular Ca2+ involvement in proliferative and apoptotic events. 

Shimizu, T., Morishima, S. and Okada, Y., 2000, Ca2+-sensing receptor-mediated regulation of volume-sensitive Cl- channels in human epithelial cells. J Physiol 528, 457-72. 

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