Control of Slc7a5 sensitivity by the voltage-sensing domain of Kv1 channels
Many voltage-dependent ion channels are regulated by accessory proteins. We recently reported powerful regulation of Kv1.2 potassium channels by the amino acid transporter Slc7a5. In this study, we report that Kv1.1 channels are also regulated by Slc7a5, albeit with different functional outcomes. In...
| Main Authors: | , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
eLife Sciences Publications Ltd
2020-11-01
|
| Series: | eLife |
| Subjects: | |
| Online Access: | https://elifesciences.org/articles/54916 |
| _version_ | 1818028558566555648 |
|---|---|
| author | Shawn M Lamothe Nazlee Sharmin Grace Silver Motoyasu Satou Yubin Hao Toru Tateno Victoria A Baronas Harley T Kurata |
| author_facet | Shawn M Lamothe Nazlee Sharmin Grace Silver Motoyasu Satou Yubin Hao Toru Tateno Victoria A Baronas Harley T Kurata |
| author_sort | Shawn M Lamothe |
| collection | DOAJ |
| description | Many voltage-dependent ion channels are regulated by accessory proteins. We recently reported powerful regulation of Kv1.2 potassium channels by the amino acid transporter Slc7a5. In this study, we report that Kv1.1 channels are also regulated by Slc7a5, albeit with different functional outcomes. In heterologous expression systems, Kv1.1 exhibits prominent current enhancement ('disinhibition') with holding potentials more negative than −120 mV. Knockdown of endogenous Slc7a5 leads to larger Kv1.1 currents and strongly attenuates the disinhibition effect, suggesting that Slc7a5 regulation of Kv1.1 involves channel inhibition that can be reversed by supraphysiological hyperpolarizing voltages. We investigated chimeric combinations of Kv1.1 and Kv1.2, demonstrating that exchange of the voltage-sensing domain controls the sensitivity and response to Slc7a5, and localize a specific position in S1 with prominent effects on Slc7a5 sensitivity. Overall, our study highlights multiple Slc7a5-sensitive Kv1 subunits, and identifies the voltage-sensing domain as a determinant of Slc7a5 modulation of Kv1 channels. |
| first_indexed | 2024-12-10T05:05:42Z |
| format | Article |
| id | doaj.art-f521d5e399a34766b3968684f92f7f68 |
| institution | Directory Open Access Journal |
| issn | 2050-084X |
| language | English |
| last_indexed | 2024-12-10T05:05:42Z |
| publishDate | 2020-11-01 |
| publisher | eLife Sciences Publications Ltd |
| record_format | Article |
| series | eLife |
| spelling | doaj.art-f521d5e399a34766b3968684f92f7f682022-12-22T02:01:16ZengeLife Sciences Publications LtdeLife2050-084X2020-11-01910.7554/eLife.54916Control of Slc7a5 sensitivity by the voltage-sensing domain of Kv1 channelsShawn M Lamothe0https://orcid.org/0000-0001-8722-2631Nazlee Sharmin1Grace Silver2Motoyasu Satou3Yubin Hao4Toru Tateno5Victoria A Baronas6Harley T Kurata7https://orcid.org/0000-0003-4357-4189Department of Pharmacology, Alberta Diabetes Institute, University of Alberta, Edmonton, CanadaSchool of Dentistry, Faculty of Medicine and Dentistry, University of Alberta, School of Dentistry, Edmonton Clinic Health Academy (ECHA), Edmonton, CanadaDepartment of Pharmacology, Alberta Diabetes Institute, University of Alberta, Edmonton, CanadaDepartment of Biochemistry, Dokkyo Medical University School of Medicine, Tochigi, Japan; Department of Medicine, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, CanadaDepartment of Pharmacology, Alberta Diabetes Institute, University of Alberta, Edmonton, CanadaDepartment of Medicine, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, CanadaDepartment of Pharmacology, Alberta Diabetes Institute, University of Alberta, Edmonton, CanadaDepartment of Pharmacology, Alberta Diabetes Institute, University of Alberta, Edmonton, CanadaMany voltage-dependent ion channels are regulated by accessory proteins. We recently reported powerful regulation of Kv1.2 potassium channels by the amino acid transporter Slc7a5. In this study, we report that Kv1.1 channels are also regulated by Slc7a5, albeit with different functional outcomes. In heterologous expression systems, Kv1.1 exhibits prominent current enhancement ('disinhibition') with holding potentials more negative than −120 mV. Knockdown of endogenous Slc7a5 leads to larger Kv1.1 currents and strongly attenuates the disinhibition effect, suggesting that Slc7a5 regulation of Kv1.1 involves channel inhibition that can be reversed by supraphysiological hyperpolarizing voltages. We investigated chimeric combinations of Kv1.1 and Kv1.2, demonstrating that exchange of the voltage-sensing domain controls the sensitivity and response to Slc7a5, and localize a specific position in S1 with prominent effects on Slc7a5 sensitivity. Overall, our study highlights multiple Slc7a5-sensitive Kv1 subunits, and identifies the voltage-sensing domain as a determinant of Slc7a5 modulation of Kv1 channels.https://elifesciences.org/articles/54916potassium channelKv1.1Kv1.2Slc7a5voltage-dependent gating |
| spellingShingle | Shawn M Lamothe Nazlee Sharmin Grace Silver Motoyasu Satou Yubin Hao Toru Tateno Victoria A Baronas Harley T Kurata Control of Slc7a5 sensitivity by the voltage-sensing domain of Kv1 channels eLife potassium channel Kv1.1 Kv1.2 Slc7a5 voltage-dependent gating |
| title | Control of Slc7a5 sensitivity by the voltage-sensing domain of Kv1 channels |
| title_full | Control of Slc7a5 sensitivity by the voltage-sensing domain of Kv1 channels |
| title_fullStr | Control of Slc7a5 sensitivity by the voltage-sensing domain of Kv1 channels |
| title_full_unstemmed | Control of Slc7a5 sensitivity by the voltage-sensing domain of Kv1 channels |
| title_short | Control of Slc7a5 sensitivity by the voltage-sensing domain of Kv1 channels |
| title_sort | control of slc7a5 sensitivity by the voltage sensing domain of kv1 channels |
| topic | potassium channel Kv1.1 Kv1.2 Slc7a5 voltage-dependent gating |
| url | https://elifesciences.org/articles/54916 |
| work_keys_str_mv | AT shawnmlamothe controlofslc7a5sensitivitybythevoltagesensingdomainofkv1channels AT nazleesharmin controlofslc7a5sensitivitybythevoltagesensingdomainofkv1channels AT gracesilver controlofslc7a5sensitivitybythevoltagesensingdomainofkv1channels AT motoyasusatou controlofslc7a5sensitivitybythevoltagesensingdomainofkv1channels AT yubinhao controlofslc7a5sensitivitybythevoltagesensingdomainofkv1channels AT torutateno controlofslc7a5sensitivitybythevoltagesensingdomainofkv1channels AT victoriaabaronas controlofslc7a5sensitivitybythevoltagesensingdomainofkv1channels AT harleytkurata controlofslc7a5sensitivitybythevoltagesensingdomainofkv1channels |