Functional coupling of TRPC2 cation channels and the calcium‐activated anion channels in rat thyroid cells: Implications for iodide homeostasis

The initial step in a synthesis of thyroid hormones is the uptake of iodide from the circulation. Iodide (I − ) is transported into thyroid cells via a Na + /I − symporter (NIS), which is electrogenic and thus sensitive to alterations in membrane potential (V m ). I − is then released to the lumen of thyroid follicles where the hormones are synthesised and stored. The mechanisms of I − release to follicle lumen are poorly characterised. Our whole‐cell voltage clamp recordings revealed the presence of a Ca 2+ activated Cl − current (CaCC) in Fisher rat thyroid cell line 5 (FRTL‐5). Transcripts of anoctamin 1 (ANO1) and anoctamin 10 (ANO10), putative molecular constituents of CaCC, were detected. The anion channels underlying CaCC are highly permeable to I − . Both niflumic acid (NFA) and 2‐aminoethyl diphenylborinate (2‐APB), antagonists of CaCC and transient receptor potential channels, respectively, inhibited CaCC. Canonical transient receptor potential channel 2 (TRPC2) is the only TRPC member present in FRTL‐5 cells. The activation rate of CaCC was markedly slower in shTRPC2 knock‐down cells, indicating that Ca 2+ entry via TRPC2 contributes to CaCC activation. The uptake of iodide was enhanced and the resting V m was more depolarised in TRPC2 knock‐down cells. We suggest that the interplay between TRPC2 and ANO1 may have dual effects on iodide transport, modulating I − release via ANO channels and I − uptake via the V m sensitive NIS. J. Cell. Physiol. 228: 814–823, 2013. © 2012 Wiley Periodicals, Inc.