Voltage-dependent K⁺ channel gating and voltage sensor toxin sensitivity depend on the mechanical state of the lipid membrane
Voltage-dependent K⁺ (Kv) channels underlie action potentials through gating conformational changes that are driven by membrane voltage. In this study of the paddle chimera Kv channel, we demonstrate that the rate of channel opening, the voltage dependence of the open probability, and the maximum ac...
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| Veröffentlicht in: | Proceedings of the National Academy of Sciences - PNAS 2008-12, Vol.105 (49), p.19276-19281 |
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| creator | Schmidt, Daniel MacKinnon, Roderick |
| description | Voltage-dependent K⁺ (Kv) channels underlie action potentials through gating conformational changes that are driven by membrane voltage. In this study of the paddle chimera Kv channel, we demonstrate that the rate of channel opening, the voltage dependence of the open probability, and the maximum achievable open probability depend on the lipid membrane environment. The activity of the voltage sensor toxin VsTx1, which interferes with voltage-dependent gating by partitioning into the membrane and binding to the channel, also depends on the membrane. Membrane environmental factors that influence channel function are divisible into two general categories: lipid compositional and mechanical state. The mechanical state can have a surprisingly large effect on the function of a voltage-dependent K⁺ channel, including its pharmacological interaction with voltage sensor toxins. The dependence of VSTx1 activity on the mechanical state of the membrane leads us to hypothesize that voltage sensor toxins exert their effect by perturbing the interaction forces that exist between the channel and the membrane. |
| doi_str_mv | 10.1073/pnas.0810187105 |
| format | Article |
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In this study of the paddle chimera Kv channel, we demonstrate that the rate of channel opening, the voltage dependence of the open probability, and the maximum achievable open probability depend on the lipid membrane environment. The activity of the voltage sensor toxin VsTx1, which interferes with voltage-dependent gating by partitioning into the membrane and binding to the channel, also depends on the membrane. Membrane environmental factors that influence channel function are divisible into two general categories: lipid compositional and mechanical state. The mechanical state can have a surprisingly large effect on the function of a voltage-dependent K⁺ channel, including its pharmacological interaction with voltage sensor toxins. The dependence of VSTx1 activity on the mechanical state of the membrane leads us to hypothesize that voltage sensor toxins exert their effect by perturbing the interaction forces that exist between the channel and the membrane.</description><identifier>ISSN: 0027-8424</identifier><identifier>EISSN: 1091-6490</identifier><identifier>DOI: 10.1073/pnas.0810187105</identifier><identifier>PMID: 19050073</identifier><language>eng</language><publisher>United States: National Academy of Sciences</publisher><subject>Animals ; Binding sites ; Biological Sciences ; Cell Membrane - drug effects ; Cell Membrane - metabolism ; Cell membranes ; Chemical composition ; Chimeras ; Electric potential ; Ion Channel Gating - drug effects ; Ion Channel Gating - physiology ; Lipid Bilayers - metabolism ; Lipids ; Membranes ; Models, Biological ; Oocytes ; Oocytes - physiology ; P branes ; Patch-Clamp Techniques ; Peptides - pharmacology ; Pipettes ; Potassium ; Potassium Channels, Voltage-Gated - physiology ; Recombinant Fusion Proteins - physiology ; Sensors ; Spider Venoms - pharmacology ; Stress, Mechanical ; Studies ; Suction ; Toxins ; Xenopus laevis</subject><ispartof>Proceedings of the National Academy of Sciences - PNAS, 2008-12, Vol.105 (49), p.19276-19281</ispartof><rights>Copyright 2008 The National Academy of Sciences of the United States of America</rights><rights>Copyright National Academy of Sciences Dec 9, 2008</rights><rights>2008 by The National Academy of Sciences of the USA</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c589t-e1dacff3ad7b187f0a695878c9d7f3a8d4815b0db72deaea6a2e4b17514fefe03</citedby><cites>FETCH-LOGICAL-c589t-e1dacff3ad7b187f0a695878c9d7f3a8d4815b0db72deaea6a2e4b17514fefe03</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Uhttp://www.pnas.org/content/105/49.cover.gif</thumbnail><linktopdf>$$Uhttps://www.jstor.org/stable/pdf/25465635$$EPDF$$P50$$Gjstor$$H</linktopdf><linktohtml>$$Uhttps://www.jstor.org/stable/25465635$$EHTML$$P50$$Gjstor$$H</linktohtml><link.rule.ids>230,314,724,777,781,800,882,27905,27906,53772,53774,57998,58231</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/19050073$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Schmidt, Daniel</creatorcontrib><creatorcontrib>MacKinnon, Roderick</creatorcontrib><title>Voltage-dependent K⁺ channel gating and voltage sensor toxin sensitivity depend on the mechanical state of the lipid membrane</title><title>Proceedings of the National Academy of Sciences - PNAS</title><addtitle>Proc Natl Acad Sci U S A</addtitle><description>Voltage-dependent K⁺ (Kv) channels underlie action potentials through gating conformational changes that are driven by membrane voltage. In this study of the paddle chimera Kv channel, we demonstrate that the rate of channel opening, the voltage dependence of the open probability, and the maximum achievable open probability depend on the lipid membrane environment. The activity of the voltage sensor toxin VsTx1, which interferes with voltage-dependent gating by partitioning into the membrane and binding to the channel, also depends on the membrane. Membrane environmental factors that influence channel function are divisible into two general categories: lipid compositional and mechanical state. The mechanical state can have a surprisingly large effect on the function of a voltage-dependent K⁺ channel, including its pharmacological interaction with voltage sensor toxins. The dependence of VSTx1 activity on the mechanical state of the membrane leads us to hypothesize that voltage sensor toxins exert their effect by perturbing the interaction forces that exist between the channel and the membrane.</description><subject>Animals</subject><subject>Binding sites</subject><subject>Biological Sciences</subject><subject>Cell Membrane - drug effects</subject><subject>Cell Membrane - metabolism</subject><subject>Cell membranes</subject><subject>Chemical composition</subject><subject>Chimeras</subject><subject>Electric potential</subject><subject>Ion Channel Gating - drug effects</subject><subject>Ion Channel Gating - physiology</subject><subject>Lipid Bilayers - metabolism</subject><subject>Lipids</subject><subject>Membranes</subject><subject>Models, Biological</subject><subject>Oocytes</subject><subject>Oocytes - physiology</subject><subject>P branes</subject><subject>Patch-Clamp Techniques</subject><subject>Peptides - pharmacology</subject><subject>Pipettes</subject><subject>Potassium</subject><subject>Potassium Channels, Voltage-Gated - physiology</subject><subject>Recombinant Fusion Proteins - physiology</subject><subject>Sensors</subject><subject>Spider Venoms - pharmacology</subject><subject>Stress, Mechanical</subject><subject>Studies</subject><subject>Suction</subject><subject>Toxins</subject><subject>Xenopus laevis</subject><issn>0027-8424</issn><issn>1091-6490</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2008</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkc9u1DAQxiMEotvCmRNgcUDikHac2HFyQUIV_0QlDlCulhNPdr3K2ovtrNpTxWvxODwJTrPqAhdOlmd-8818-rLsCYVTCqI821oVTqGmQGtBgd_LFhQamlesgfvZAqAQec0KdpQdh7AGgIbX8DA7og1wSPOL7OabG6JaYq5xi1ajjeTTrx8_SbdS1uJAlioauyTKarKbSRLQBudJdFfG3n5MNDsTr8ksQZwlcYVkg5OG6dRAQlQRietv64PZGp26m9Yri4-yB70aAj7evyfZ5bu3X88_5Bef3388f3ORd7xuYo5Uq67vS6VFm6z2oKpkRdRdo0Wq1prVlLegW1FoVKgqVSBrqeCU9dgjlCfZ61l3O7Yb1F0y6tUgt95slL-WThn5d8ealVy6nSwqygQvksDLvYB330cMUW5M6HAYkgk3Blk1tQDBeAJf_AOu3ehtMicLoCXjjWAJOpuhzrsQPPZ3l1CQU7JySlYekk0Tz_40cOD3USaA7IFp8iDHJWsSVYgqIa_-g8h-HIaIVzGxT2d2HaLzd3DBWcWrcrrn-dzvlZNq6U2Ql18mg0B5yiZt-w0L3c-Z</recordid><startdate>20081209</startdate><enddate>20081209</enddate><creator>Schmidt, Daniel</creator><creator>MacKinnon, Roderick</creator><general>National Academy of Sciences</general><general>National Acad Sciences</general><scope>FBQ</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7QG</scope><scope>7QL</scope><scope>7QP</scope><scope>7QR</scope><scope>7SN</scope><scope>7SS</scope><scope>7T5</scope><scope>7TK</scope><scope>7TM</scope><scope>7TO</scope><scope>7U9</scope><scope>8FD</scope><scope>C1K</scope><scope>FR3</scope><scope>H94</scope><scope>M7N</scope><scope>P64</scope><scope>RC3</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>20081209</creationdate><title>Voltage-dependent K⁺ channel gating and voltage sensor toxin sensitivity depend on the mechanical state of the lipid membrane</title><author>Schmidt, Daniel ; MacKinnon, Roderick</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c589t-e1dacff3ad7b187f0a695878c9d7f3a8d4815b0db72deaea6a2e4b17514fefe03</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2008</creationdate><topic>Animals</topic><topic>Binding sites</topic><topic>Biological Sciences</topic><topic>Cell Membrane - drug effects</topic><topic>Cell Membrane - metabolism</topic><topic>Cell membranes</topic><topic>Chemical composition</topic><topic>Chimeras</topic><topic>Electric potential</topic><topic>Ion Channel Gating - drug effects</topic><topic>Ion Channel Gating - physiology</topic><topic>Lipid Bilayers - metabolism</topic><topic>Lipids</topic><topic>Membranes</topic><topic>Models, Biological</topic><topic>Oocytes</topic><topic>Oocytes - physiology</topic><topic>P branes</topic><topic>Patch-Clamp Techniques</topic><topic>Peptides - pharmacology</topic><topic>Pipettes</topic><topic>Potassium</topic><topic>Potassium Channels, Voltage-Gated - physiology</topic><topic>Recombinant Fusion Proteins - physiology</topic><topic>Sensors</topic><topic>Spider Venoms - pharmacology</topic><topic>Stress, Mechanical</topic><topic>Studies</topic><topic>Suction</topic><topic>Toxins</topic><topic>Xenopus laevis</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Schmidt, Daniel</creatorcontrib><creatorcontrib>MacKinnon, Roderick</creatorcontrib><collection>AGRIS</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Animal Behavior Abstracts</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Calcium & Calcified Tissue Abstracts</collection><collection>Chemoreception Abstracts</collection><collection>Ecology Abstracts</collection><collection>Entomology Abstracts (Full archive)</collection><collection>Immunology Abstracts</collection><collection>Neurosciences Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Oncogenes and Growth Factors Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Technology Research Database</collection><collection>Environmental Sciences and Pollution Management</collection><collection>Engineering Research Database</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Proceedings of the National Academy of Sciences - PNAS</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Schmidt, Daniel</au><au>MacKinnon, Roderick</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Voltage-dependent K⁺ channel gating and voltage sensor toxin sensitivity depend on the mechanical state of the lipid membrane</atitle><jtitle>Proceedings of the National Academy of Sciences - PNAS</jtitle><addtitle>Proc Natl Acad Sci U S A</addtitle><date>2008-12-09</date><risdate>2008</risdate><volume>105</volume><issue>49</issue><spage>19276</spage><epage>19281</epage><pages>19276-19281</pages><issn>0027-8424</issn><eissn>1091-6490</eissn><abstract>Voltage-dependent K⁺ (Kv) channels underlie action potentials through gating conformational changes that are driven by membrane voltage. In this study of the paddle chimera Kv channel, we demonstrate that the rate of channel opening, the voltage dependence of the open probability, and the maximum achievable open probability depend on the lipid membrane environment. The activity of the voltage sensor toxin VsTx1, which interferes with voltage-dependent gating by partitioning into the membrane and binding to the channel, also depends on the membrane. Membrane environmental factors that influence channel function are divisible into two general categories: lipid compositional and mechanical state. The mechanical state can have a surprisingly large effect on the function of a voltage-dependent K⁺ channel, including its pharmacological interaction with voltage sensor toxins. The dependence of VSTx1 activity on the mechanical state of the membrane leads us to hypothesize that voltage sensor toxins exert their effect by perturbing the interaction forces that exist between the channel and the membrane.</abstract><cop>United States</cop><pub>National Academy of Sciences</pub><pmid>19050073</pmid><doi>10.1073/pnas.0810187105</doi><tpages>6</tpages><oa>free_for_read</oa></addata></record> |
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| source | MEDLINE; Jstor Complete Legacy; PubMed Central; Alma/SFX Local Collection; Free Full-Text Journals in Chemistry |
| subjects | Animals Binding sites Biological Sciences Cell Membrane - drug effects Cell Membrane - metabolism Cell membranes Chemical composition Chimeras Electric potential Ion Channel Gating - drug effects Ion Channel Gating - physiology Lipid Bilayers - metabolism Lipids Membranes Models, Biological Oocytes Oocytes - physiology P branes Patch-Clamp Techniques Peptides - pharmacology Pipettes Potassium Potassium Channels, Voltage-Gated - physiology Recombinant Fusion Proteins - physiology Sensors Spider Venoms - pharmacology Stress, Mechanical Studies Suction Toxins Xenopus laevis |
| title | Voltage-dependent K⁺ channel gating and voltage sensor toxin sensitivity depend on the mechanical state of the lipid membrane |
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