External Ca2+ regulates polycystin-2 (TRPP2) cation currents in LLC-PK1 renal epithelial cells.

SUZUKI K; SCARINCI N; DAI XQ; SUZUKI K; CANTIELLO HF; CANTERO MD; SCARINCI N; MORSUCCI DC; SMOLER M; DAI XQ; SORIA G; PEREZ PL; CANTERO MD; CANTIELLO HF; SMOLER M; MORSUCCI DC; SORIA G; PEREZ PL

EXPERIMENTAL CELL RESEARCH

ELSEVIER INC

Lugar: Amsterdam ; Año: 2017 p. 50 - 61

0014-4827

Polycystin-2 (PC2, TRPP2) is a nonselective cation channel whose dysfunction is associated with the onset ofautosomal dominant polycystic kidney disease (ADPKD). PC2 contributes to Ca2+ transport and cell signaling inrenal epithelia and other tissues. Little is known however, as to the external Ca2+ regulation of PC2 channelfunction. In this study, we explored the effect of external Ca2+ on endogenous PC2 in wild type LLC-PK1 renalepithelial cells. We obtained whole cell currents at different external Ca2+ concentrations, and observed that thebasal whole cell conductance in normal Ca2+(1.2 mM), decreased by 30.2% in zero (nominal) Ca2+ andconversely, increased by 38% in high external Ca2+(6.2 mM). The high Ca2+-increased whole cell currents werecompletely inhibited by either PC2 gene silencing, or intracellular dialysis with active, but not denatured byboiling, PC2 antibody. Exposure of cells to high Ca2+ was also associated with relocation of PC2 to the plasmamembrane. To explore whether a Ca2+ sensing receptor (CaSR) was implicated in the external Ca2+ modulationof PC2 currents, we tested the effect of the CaSR agonists, spermine and the calcimimetic R-568, which largelymimicked the effect of high Ca2+ under Ca2+-free conditions. The CaSR agonist gentamicin also increased thePC2 currents in the presence of normal Ca2+. The presence of CaSR was confirmed by immunocytochemistry,which partially colocalized with the intracellular PC2 protein, in an external Ca2+-dependent manner. The datasupport a novel Ca2+ sensing mechanism for PC2 expression and functional regulation in renal epithelial cells.