Objective: Calcium activated chloride currents (I_Cl,Ca) are known to play important roles in cell physiology. In 2008, 3 different groups (Yang et al., 2008; Caputo et al., 2008; Schroeder et al., 2008), independently identified the protein TMEM16A as being associated with I_Cl,Ca. The TMEM16 family consist of 10 members, TMEM16A-K, several of which the functions are yet to be elucidated. Methods: We have cloned and expressed mouse TMEM16F and analyzed its biophysical properties using whole cell patch recording. Results: When over expressed in HEK293 cells, mTMEM16F (anoctamin 6) was found to introduce an outwardly rectifying I_Cl,Ca but not a volume-sensitive current. The current activates time-dependently at high positive potentials, has an anion selectivity sequence of SCN^- > I^- > Br^- > Cl^- > Asp^- and is sensitive to tamoxifen > niflumic acid > NS3728 > DIDS. Mutation to glutamic acid of R592, K616 and K636, the homologue amino acids which in TMEM16A has been suggested to affect channel anion selectivity, completely abolished the I_Cl,Ca. In addition, we found that stable knock-down of mTMEM16F in EATC reduced I_Cl,Ca significantly. Conclusion: mTMEM16F appears to convey a I_Cl,Ca which may play important roles in cell physiology.

Caputo A, Caci E, Ferrera L et al. Science 2008; 322:590-594.

Schroeder BC, Cheng T, Jan YN, Jan LY. Cell 2008; 134:1019-1029.

Yang YD, Cho H, Koo JY et al. Nature 2008; 455:1210-1215.