The asparagine 533 residue in the outer pore loop region of the mouse PKD2L1 channel is essential for its voltage‐dependent inactivation
Voltage‐dependent inactivation of ion channels contributes to the regulation of the membrane potential of excitable cells. Mouse polycystic kidney disease 2‐like 1 (PKD2L1) forms voltage‐dependent nonselective cation channels, which are activated but subsequently inactivated in response to membrane...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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Wiley
2017-09-01
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| Series: | FEBS Open Bio |
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| Online Access: | https://doi.org/10.1002/2211-5463.12273 |
| _version_ | 1828192622867382272 |
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| author | Takahiro Shimizu Taiga Higuchi Toshihiro Toba Chie Ohno Takuto Fujii Bernd Nilius Hideki Sakai |
| author_facet | Takahiro Shimizu Taiga Higuchi Toshihiro Toba Chie Ohno Takuto Fujii Bernd Nilius Hideki Sakai |
| author_sort | Takahiro Shimizu |
| collection | DOAJ |
| description | Voltage‐dependent inactivation of ion channels contributes to the regulation of the membrane potential of excitable cells. Mouse polycystic kidney disease 2‐like 1 (PKD2L1) forms voltage‐dependent nonselective cation channels, which are activated but subsequently inactivated in response to membrane depolarization. Here, we found that the mutation of an asparagine 533 residue (N533Q) in the outer pore loop region of PKD2L1 caused a marked increase in outward currents induced by depolarization. In addition, the tail current analysis demonstrated that the N533Q mutants are activated during depolarization but the subsequent inactivation does not occur. Interestingly, the N533Q mutants lacked the channel activation triggered by the removal of stimuli such as extracellular alkalization and heating. Our findings suggest that the N533 residue in the outer pore loop region of PKD2L1 has a key role in the voltage‐dependent channel inactivation. |
| first_indexed | 2024-04-12T08:57:16Z |
| format | Article |
| id | doaj.art-9b4c822774004391a51b5aa8190bee86 |
| institution | Directory Open Access Journal |
| issn | 2211-5463 |
| language | English |
| last_indexed | 2024-04-12T08:57:16Z |
| publishDate | 2017-09-01 |
| publisher | Wiley |
| record_format | Article |
| series | FEBS Open Bio |
| spelling | doaj.art-9b4c822774004391a51b5aa8190bee862022-12-22T03:39:20ZengWileyFEBS Open Bio2211-54632017-09-01791392140110.1002/2211-5463.12273The asparagine 533 residue in the outer pore loop region of the mouse PKD2L1 channel is essential for its voltage‐dependent inactivationTakahiro Shimizu0Taiga Higuchi1Toshihiro Toba2Chie Ohno3Takuto Fujii4Bernd Nilius5Hideki Sakai6Department of Pharmaceutical Physiology Graduate School of Medicine and Pharmaceutical Sciences University of Toyama JapanDepartment of Pharmaceutical Physiology Graduate School of Medicine and Pharmaceutical Sciences University of Toyama JapanDepartment of Pharmaceutical Physiology Graduate School of Medicine and Pharmaceutical Sciences University of Toyama JapanDepartment of Pharmaceutical Physiology Graduate School of Medicine and Pharmaceutical Sciences University of Toyama JapanDepartment of Pharmaceutical Physiology Graduate School of Medicine and Pharmaceutical Sciences University of Toyama JapanLaboratory of Ion Channel Research Department of Cellular and Molecular Medicine KU Leuven BelgiumDepartment of Pharmaceutical Physiology Graduate School of Medicine and Pharmaceutical Sciences University of Toyama JapanVoltage‐dependent inactivation of ion channels contributes to the regulation of the membrane potential of excitable cells. Mouse polycystic kidney disease 2‐like 1 (PKD2L1) forms voltage‐dependent nonselective cation channels, which are activated but subsequently inactivated in response to membrane depolarization. Here, we found that the mutation of an asparagine 533 residue (N533Q) in the outer pore loop region of PKD2L1 caused a marked increase in outward currents induced by depolarization. In addition, the tail current analysis demonstrated that the N533Q mutants are activated during depolarization but the subsequent inactivation does not occur. Interestingly, the N533Q mutants lacked the channel activation triggered by the removal of stimuli such as extracellular alkalization and heating. Our findings suggest that the N533 residue in the outer pore loop region of PKD2L1 has a key role in the voltage‐dependent channel inactivation.https://doi.org/10.1002/2211-5463.12273channelinactivationPKD2L1transient receptor potentialTRPP3 |
| spellingShingle | Takahiro Shimizu Taiga Higuchi Toshihiro Toba Chie Ohno Takuto Fujii Bernd Nilius Hideki Sakai The asparagine 533 residue in the outer pore loop region of the mouse PKD2L1 channel is essential for its voltage‐dependent inactivation FEBS Open Bio channel inactivation PKD2L1 transient receptor potential TRPP3 |
| title | The asparagine 533 residue in the outer pore loop region of the mouse PKD2L1 channel is essential for its voltage‐dependent inactivation |
| title_full | The asparagine 533 residue in the outer pore loop region of the mouse PKD2L1 channel is essential for its voltage‐dependent inactivation |
| title_fullStr | The asparagine 533 residue in the outer pore loop region of the mouse PKD2L1 channel is essential for its voltage‐dependent inactivation |
| title_full_unstemmed | The asparagine 533 residue in the outer pore loop region of the mouse PKD2L1 channel is essential for its voltage‐dependent inactivation |
| title_short | The asparagine 533 residue in the outer pore loop region of the mouse PKD2L1 channel is essential for its voltage‐dependent inactivation |
| title_sort | asparagine 533 residue in the outer pore loop region of the mouse pkd2l1 channel is essential for its voltage dependent inactivation |
| topic | channel inactivation PKD2L1 transient receptor potential TRPP3 |
| url | https://doi.org/10.1002/2211-5463.12273 |
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