Abstract
TMEM16F is activated by elevated intracellular Ca2+, and functions as a small-conductance ion channel and as a phospholipid scramblase. In contrast to its paralogs, the TMEM16A/B calcium-activated chloride channels, mouse TMEM16F has been reported as a cation-, anion-, or non-selective ion channel, without a definite conclusion. Starting with the Q559K mutant that shows no current rundown and less outward rectification in excised patch, we found that the channel shifted its ion selectivity in response to the change of intracellular Ca2+ concentration, with an increased permeability ratio of Cl- to Na+ (PCl-/PNa+) at a higher Ca2+ level. The gradual shift of relative ion permeability did not correlate with the channel activation state. Instead, it was indicative of an alteration of electrostatic field in the permeation pathway. The dynamic change of ion selectivity suggests a charge-screening mechanism for TMEM16F ion conduction, and it provides hints to the study of TMEM16F physiological functions.
Article and author information
Author details
Funding
National Institute of Neurological Disorders and Stroke (R01NS069229)
- Lily Yeh Jan
Jane Coffin Childs Memorial Fund for Medical Research
- Tina W Han
Eunice Kennedy Shriver National Institute of Child Health and Human Development (F32HD089639)
- Mu He
Howard Hughes Medical Institute
- Yuh Nung Jan
- Lily Yeh Jan
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Reviewing Editor
- Kenton Jon Swartz, National Institute of Neurological Disorders and Stroke, National Institutes of Health, United States
Publication history
- Received: January 14, 2019
- Accepted: July 17, 2019
- Accepted Manuscript published: July 18, 2019 (version 1)
- Version of Record published: August 12, 2019 (version 2)
Copyright
© 2019, Ye et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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