Journal
JOURNAL OF GENERAL PHYSIOLOGY
Volume 141, Issue 5, Pages 585-600Publisher
ROCKEFELLER UNIV PRESS
DOI: 10.1085/jgp.201210861
Keywords
-
Categories
Funding
- Danish Council for Independent Research/Natural Sciences [09-064182, 10-085373]
- Lundbeck Foundation [J Nr R32-A3102]
- Carlsberg Foundation [2008-01-0639]
Ask authors/readers for more resources
Members of the TMEM16 (Anoctamin) family of membrane proteins have been shown to be essential constituents of the Ca2+-activated Cl- channel (CaCC) in many cell types. In this study, we have investigated the electrophysiological properties of mouse TMEM16F. Heterologous expression of TMEM16F in HEK293 cells resulted in plasma membrane localization and an outwardly rectifying I-Cl,I-Ca that was activated with a delay of several minutes. Furthermore, a significant Na+ current was activated, and the two permeabilities were correlated according to P-Na = 0.3 P-Cl. The current showed an EC50 of 100 mu M intracellular free Ca2+ concentration and an Eisenman type 1 anion selectivity sequence of P-SCN > P-I > P-Br > P-Cl > P-Asp. The mTMEM16F-associated I-Cl,I-Ca was abolished in one mutant of the putative pore region (R592E) but retained in two other mutants (K616E and R636E). The mutant K616E had a lower relative permeability to iodide, and the mutant R636E had an altered anion selectivity sequence (P-SCN = P-I = P-Br = P-Cl > P-Asp). Our data provide evidence that TMEM16F constitutes a Ca2+-activated anion channel or a pore-forming subunit of an anion channel with properties distinct from TMEM16A.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available