Anion and Cation Permeability of the Mouse TMEM16F Calcium-Activated Channel
TMEM16F is involved in several physiological processes, such as blood coagulation, bone development and virus infections. This protein acts both as a Ca<sup>2+</sup>-dependent phospholipid scramblase and a Ca<sup>2+</sup>-activated ion channel but several studies have reporte...
| Main Authors: | , , |
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| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2021-08-01
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| Series: | International Journal of Molecular Sciences |
| Subjects: | |
| Online Access: | https://www.mdpi.com/1422-0067/22/16/8578 |
| Summary: | TMEM16F is involved in several physiological processes, such as blood coagulation, bone development and virus infections. This protein acts both as a Ca<sup>2+</sup>-dependent phospholipid scramblase and a Ca<sup>2+</sup>-activated ion channel but several studies have reported conflicting results about the ion selectivity of the TMEM16F-mediated current. Here, we have performed a detailed side-by-side comparison of the ion selectivity of TMEM16F using the whole-cell and inside-out excised patch configurations to directly compare the results. In inside-out configuration, Ca<sup>2+</sup>-dependent activation was fast and the TMEM16F-mediated current was activated in a few milliseconds, while in whole-cell recordings full activation required several minutes. We determined the relative permeability between Na<sup>+</sup> and Cl¯ (P<sub>Na</sub>/P<sub>Cl</sub>) using the dilution method in both configurations. The TMEM16F-mediated current was highly nonselective, but there were differences depending on the configuration of the recordings. In whole-cell recordings, P<sub>Na</sub>/P<sub>Cl</sub> was approximately 0.5, indicating a slight preference for Cl¯ permeation. In contrast, in inside-out experiments the TMEM16F channel showed a higher permeability for Na<sup>+</sup> with P<sub>Na</sub>/P<sub>Cl</sub> reaching 3.7. Our results demonstrate that the time dependence of Ca<sup>2+</sup> activation and the ion selectivity of TMEM16F depend on the recording configuration. |
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| ISSN: | 1661-6596 1422-0067 |