Investigation of K2P channel permeation and gating
<p>The ability to conduct potassium ions (K<sup>+</sup>) selectively in the abundant presence of other ion species is crucial to the function of K<sup>+</sup> channels. While the mechanism of ion selectivity has been an in- tensely studied and debated topic, the protein...
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| Format: | Thesis |
| Language: | English |
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2019
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| _version_ | 1797076403990036480 |
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| author | Conrad, L |
| author2 | Tucker, S |
| author_facet | Tucker, S Conrad, L |
| author_sort | Conrad, L |
| collection | OXFORD |
| description | <p>The ability to conduct potassium ions (K<sup>+</sup>) selectively in the abundant presence of other ion species is crucial to the function of K<sup>+</sup> channels. While the mechanism of ion selectivity has been an in- tensely studied and debated topic, the protein structure responsible for ion-selectivity has long been identified as the so called selectivity filter (SF). The SF also doubles as the principal regulatory element (gate) in many K<sup>+</sup> channels.</p>
<p>In this project several phenomena related to the permeation, selectivity and gating at the SF of two-pore-domain K<sup>+</sup> channels (K2P channels) were investigated. Firstly, the effect of mutations at the intracellular entrance of the TASK3 (TWIK-related acid sensitive K<sup>+</sup> 3) channel SF were studied. Secondly, the mechanism of pharmacological activation of the TREK2 (TWIK related K<sup>+</sup> channel 2) SF gate was probed on a single molecule level. Channel activation was found to be conferred by a change to the electrostatic milieu at the SF entrance. </p>
<p>Following from this electrostatic mechanism the dependence of gating on salt concentration (ionic strength) was probed. Here an unusual property emerged: TREK channels close in the presence of high ionic strength. </p>
<p>Finally, evidence was found that TREK2 may change its ion- selectivity in the context of voltage-dependent gating. This result suggests that TREK2 may have a stimulating effect on cellular exciteability, which is a novel and atypical property for a K<sup>+</sup> channel</p> |
| first_indexed | 2024-03-07T00:03:21Z |
| format | Thesis |
| id | oxford-uuid:76bac652-da62-49c9-abe3-a8d30a129393 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T00:03:21Z |
| publishDate | 2019 |
| record_format | dspace |
| spelling | oxford-uuid:76bac652-da62-49c9-abe3-a8d30a1293932022-03-26T20:18:10ZInvestigation of K2P channel permeation and gatingThesishttp://purl.org/coar/resource_type/c_db06uuid:76bac652-da62-49c9-abe3-a8d30a129393EnglishORA Deposit2019Conrad, LTucker, SCarpenter, L<p>The ability to conduct potassium ions (K<sup>+</sup>) selectively in the abundant presence of other ion species is crucial to the function of K<sup>+</sup> channels. While the mechanism of ion selectivity has been an in- tensely studied and debated topic, the protein structure responsible for ion-selectivity has long been identified as the so called selectivity filter (SF). The SF also doubles as the principal regulatory element (gate) in many K<sup>+</sup> channels.</p> <p>In this project several phenomena related to the permeation, selectivity and gating at the SF of two-pore-domain K<sup>+</sup> channels (K2P channels) were investigated. Firstly, the effect of mutations at the intracellular entrance of the TASK3 (TWIK-related acid sensitive K<sup>+</sup> 3) channel SF were studied. Secondly, the mechanism of pharmacological activation of the TREK2 (TWIK related K<sup>+</sup> channel 2) SF gate was probed on a single molecule level. Channel activation was found to be conferred by a change to the electrostatic milieu at the SF entrance. </p> <p>Following from this electrostatic mechanism the dependence of gating on salt concentration (ionic strength) was probed. Here an unusual property emerged: TREK channels close in the presence of high ionic strength. </p> <p>Finally, evidence was found that TREK2 may change its ion- selectivity in the context of voltage-dependent gating. This result suggests that TREK2 may have a stimulating effect on cellular exciteability, which is a novel and atypical property for a K<sup>+</sup> channel</p> |
| spellingShingle | Conrad, L Investigation of K2P channel permeation and gating |
| title | Investigation of K2P channel permeation and gating |
| title_full | Investigation of K2P channel permeation and gating |
| title_fullStr | Investigation of K2P channel permeation and gating |
| title_full_unstemmed | Investigation of K2P channel permeation and gating |
| title_short | Investigation of K2P channel permeation and gating |
| title_sort | investigation of k2p channel permeation and gating |
| work_keys_str_mv | AT conradl investigationofk2pchannelpermeationandgating |