title: Functional coupling of TRPC2 cation channels and the calcium-activated anion channels in rat thyroid cells: implications for iodide homeostasis.
abstract: 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.
authors.affiliation: Department of Biosciences, Åbo Akademi University, Turku, Finland.
authors.forename: Tero M
authors.initials: TM
authors.lastname: Viitanen
authors.forename: Pramod
authors.initials: P
authors.lastname: Sukumaran
authors.forename: Christoffer
authors.initials: C
authors.lastname: Löf
authors.forename: Kid
authors.initials: K
authors.lastname: Törnquist
mesh_terms: D000818:Animals; D000838:Anions / Q000378:metabolism; D000075369:Anoctamin-1; D001896:Boron Compounds / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D002460:Cell Line; D018118:Chloride Channels / Q000378:metabolism*; D002712:Chlorides / Q000378:metabolism; D006706:Homeostasis / Q000187:drug effects / Q000502:physiology*; D007454:Iodides / Q000378:metabolism*; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D008565:Membrane Proteins / Q000037:antagonists & inhibitors / Q000187:drug effects / Q000378:metabolism; D009544:Niflumic Acid / Q000494:pharmacology; D051381:Rats; D050052:TRPC Cation Channels / Q000037:antagonists & inhibitors / Q000378:metabolism*; D013961:Thyroid Gland / Q000187:drug effects / Q000378:metabolism*; D050994:Voltage-Dependent Anion Channels / Q000378:metabolism*
chemical_list: C538758:2-aminoethyl diphenylborinate; C552942:ANO1 protein, rat; D000838:Anions; D000075369:Anoctamin-1; D001896:Boron Compounds; D018118:Chloride Channels; D002712:Chlorides; D007454:Iodides; D008565:Membrane Proteins; D050052:TRPC Cation Channels; C491857:Trpc2 protein, rat; D050994:Voltage-Dependent Anion Channels; D009544:Niflumic Acid; D002118:Calcium