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 (Vm). 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 Ca2+ 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 Ca2+ entry via TRPC2 contributes to CaCC activation. The uptake of iodide was enhanced and the resting Vm 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 Vm sensitive NIS. J. Cell. Physiol. 228: 814–823, 2013. © 2012 Wiley Periodicals, Inc.