Regulation of the epithelial Ca ²⁺ channel TRPV5 by the NHE regulating factor NHERF2 and the serum and glucocorticoid inducible kinase isoforms SGK1 and SGK3 expressed in xenopus oocytes

The epithelial Ca ²⁺ channel TRPV5 (ECaC1) plays a key role in renal and intestinal Ca ²⁺ (re)absorption and is thus regulated by 1,25(OH) ₂D ₃. The present study aims to explore whether TRPV5 is regulated by the serum and glucocorticoid inducible kinase SGK1, a kinase transcriptionally upregulated by 1,25(OH) ₂D ₃. To this end cRNA encoding TRPV5 has been injected into Xenopus oocytes with or without additional injection of SGK1, its isoforms SGK2 and SGK3, constitutively active ^S422DSGK1, inactive ^K127NSGK1, constitutively active ^T308D,S473DPKB and/or the Na ⁺/H ⁺ exchanger regulating factor NHERF2. In Xenopus laevis oocytes expression of TRPV5 increases uptake of tracer Ca ²⁺ and induces a Ca ²⁺ current (I _Ca). In the presence of Cl ^-, TRPV5 mediated Ca ²⁺ entry leads to secondary activation of Ca ²⁺-sensitive Cl ^- channels (ICl(Ca)). Coexpression of TRPV5 with both ^S422DSGK1 and NHERF2 stimulates tracer Ca ²⁺ entry, I _Ca and I _Cl(Ca). The effect of ^S422DSGK1 on TRPV5 and NHERF2 expressing oocytes is mimicked by SGK1 and SGK3, but not by SGK2, constitutively active ^T308D,S473DPKB or inactive ^K127NSGK1. The observations suggest that SGK1, SGK3 and NHERF2 regulate TRPV5 and are thus likely to participate in the regulation of calcium homeostasis.