Protein kinase C co‐expression and the effects of halothane on rat skeletal muscle sodium channels
Voltage‐gated Na channels, which are potential targets for general anaesthetics, are substrates for PKC, which phosphorylates a conserved site in the channel inactivation gate. We investigated the idea that PKC modulates the effect of volatile anaesthetics on Na channels via phosphorylation of this...
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| Veröffentlicht in: | British journal of pharmacology 1999-11, Vol.128 (5), p.989-998 |
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| creator | Mounsey, J Paul Patel, Manoj K Mistry, Dilaawar John, J Edward Moorman, J Randall |
| description | Voltage‐gated Na channels, which are potential targets for general anaesthetics, are substrates for PKC, which phosphorylates a conserved site in the channel inactivation gate. We investigated the idea that PKC modulates the effect of volatile anaesthetics on Na channels via phosphorylation of this inactivation gate site.
Na currents through rat skeletal muscle Na channel α‐subunits expressed in Xenopus oocytes were measured by two‐microelectrode voltage clamp in the presence of the volatile anaesthetic agent halothane (2‐bromo‐2‐chloro‐1,1,1‐trifluroethane). PKC activity was modulated by co‐expression of a constitutively active PKC α‐isozyme.
Halothane (0.4 mM) had no effect on Na currents. With co‐expression of PKC, however, halothane dose‐dependently enhanced the rate of Na current decay and caused a small, but statistically significant reduction in Na current amplitude.
The enhancement of Na current decay was absent in a Na channel mutant in which the inactivation gate phosphorylation site was disabled. Effects of halothane on amplitude were independent of this mutation.
Co‐expression of a PKC α‐isozyme permits an effect of halothane to hasten current decay and reduce current amplitude, at least in part through interaction with the inactivation gate phosphorylation site. We speculate that the interaction between halothane and Na channels is direct, and facilitated by PKC activity and by phosphorylation of a site in the channel inactivation gate.
British Journal of Pharmacology (1999) 128, 989–998; doi:10.1038/sj.bjp.0702877 |
| doi_str_mv | 10.1038/sj.bjp.0702877 |
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Na currents through rat skeletal muscle Na channel α‐subunits expressed in Xenopus oocytes were measured by two‐microelectrode voltage clamp in the presence of the volatile anaesthetic agent halothane (2‐bromo‐2‐chloro‐1,1,1‐trifluroethane). PKC activity was modulated by co‐expression of a constitutively active PKC α‐isozyme.
Halothane (0.4 mM) had no effect on Na currents. With co‐expression of PKC, however, halothane dose‐dependently enhanced the rate of Na current decay and caused a small, but statistically significant reduction in Na current amplitude.
The enhancement of Na current decay was absent in a Na channel mutant in which the inactivation gate phosphorylation site was disabled. Effects of halothane on amplitude were independent of this mutation.
Co‐expression of a PKC α‐isozyme permits an effect of halothane to hasten current decay and reduce current amplitude, at least in part through interaction with the inactivation gate phosphorylation site. We speculate that the interaction between halothane and Na channels is direct, and facilitated by PKC activity and by phosphorylation of a site in the channel inactivation gate.
British Journal of Pharmacology (1999) 128, 989–998; doi:10.1038/sj.bjp.0702877</description><identifier>ISSN: 0007-1188</identifier><identifier>EISSN: 1476-5381</identifier><identifier>DOI: 10.1038/sj.bjp.0702877</identifier><identifier>PMID: 10556936</identifier><identifier>CODEN: BJPCBM</identifier><language>eng</language><publisher>Oxford, UK: Blackwell Publishing Ltd</publisher><subject>Anesthetics, Inhalation - pharmacology ; Anesthetics. Neuromuscular blocking agents ; Animals ; Biological and medical sciences ; halothane ; Halothane - pharmacology ; Isoenzymes - biosynthesis ; Kinetics ; Medical sciences ; Microelectrodes ; Muscle, Skeletal - drug effects ; Muscle, Skeletal - metabolism ; Na channels ; Neuropharmacology ; Oocytes - drug effects ; Oocytes - metabolism ; Pharmacology. Drug treatments ; protein kinase C ; Protein Kinase C - biosynthesis ; Rats ; RNA, Messenger - biosynthesis ; Sodium Channel Blockers ; Sodium Channels - drug effects ; Sodium Channels - metabolism ; Xenopus laevis</subject><ispartof>British journal of pharmacology, 1999-11, Vol.128 (5), p.989-998</ispartof><rights>1999 British Pharmacological Society</rights><rights>2000 INIST-CNRS</rights><rights>Copyright 1999, Nature Publishing Group 1999 Nature Publishing Group</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c4846-6fe1b9d80a6e75671ea64cd7a8c3a641538d18360ef1230d5f6718fb8b20b5693</citedby><cites>FETCH-LOGICAL-c4846-6fe1b9d80a6e75671ea64cd7a8c3a641538d18360ef1230d5f6718fb8b20b5693</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC1571721/pdf/$$EPDF$$P50$$Gpubmedcentral$$H</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC1571721/$$EHTML$$P50$$Gpubmedcentral$$H</linktohtml><link.rule.ids>230,314,727,780,784,885,1416,1432,27923,27924,45573,45574,46408,46832,53790,53792</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=1191605$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/10556936$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Mounsey, J Paul</creatorcontrib><creatorcontrib>Patel, Manoj K</creatorcontrib><creatorcontrib>Mistry, Dilaawar</creatorcontrib><creatorcontrib>John, J Edward</creatorcontrib><creatorcontrib>Moorman, J Randall</creatorcontrib><title>Protein kinase C co‐expression and the effects of halothane on rat skeletal muscle sodium channels</title><title>British journal of pharmacology</title><addtitle>Br J Pharmacol</addtitle><description>Voltage‐gated Na channels, which are potential targets for general anaesthetics, are substrates for PKC, which phosphorylates a conserved site in the channel inactivation gate. We investigated the idea that PKC modulates the effect of volatile anaesthetics on Na channels via phosphorylation of this inactivation gate site.
Na currents through rat skeletal muscle Na channel α‐subunits expressed in Xenopus oocytes were measured by two‐microelectrode voltage clamp in the presence of the volatile anaesthetic agent halothane (2‐bromo‐2‐chloro‐1,1,1‐trifluroethane). PKC activity was modulated by co‐expression of a constitutively active PKC α‐isozyme.
Halothane (0.4 mM) had no effect on Na currents. With co‐expression of PKC, however, halothane dose‐dependently enhanced the rate of Na current decay and caused a small, but statistically significant reduction in Na current amplitude.
The enhancement of Na current decay was absent in a Na channel mutant in which the inactivation gate phosphorylation site was disabled. Effects of halothane on amplitude were independent of this mutation.
Co‐expression of a PKC α‐isozyme permits an effect of halothane to hasten current decay and reduce current amplitude, at least in part through interaction with the inactivation gate phosphorylation site. We speculate that the interaction between halothane and Na channels is direct, and facilitated by PKC activity and by phosphorylation of a site in the channel inactivation gate.
British Journal of Pharmacology (1999) 128, 989–998; doi:10.1038/sj.bjp.0702877</description><subject>Anesthetics, Inhalation - pharmacology</subject><subject>Anesthetics. Neuromuscular blocking agents</subject><subject>Animals</subject><subject>Biological and medical sciences</subject><subject>halothane</subject><subject>Halothane - pharmacology</subject><subject>Isoenzymes - biosynthesis</subject><subject>Kinetics</subject><subject>Medical sciences</subject><subject>Microelectrodes</subject><subject>Muscle, Skeletal - drug effects</subject><subject>Muscle, Skeletal - metabolism</subject><subject>Na channels</subject><subject>Neuropharmacology</subject><subject>Oocytes - drug effects</subject><subject>Oocytes - metabolism</subject><subject>Pharmacology. Drug treatments</subject><subject>protein kinase C</subject><subject>Protein Kinase C - biosynthesis</subject><subject>Rats</subject><subject>RNA, Messenger - biosynthesis</subject><subject>Sodium Channel Blockers</subject><subject>Sodium Channels - drug effects</subject><subject>Sodium Channels - metabolism</subject><subject>Xenopus laevis</subject><issn>0007-1188</issn><issn>1476-5381</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1999</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkbFuFDEYhC0EIkegpUQuULq92Otb29sgkRMQpEikgNryen9zvnjXh_9dSDoegWfkSfDpTiRUVLY0n2c8GkJecrbkTOhz3C677W7JFKu1Uo_Igq-UrBqh-WOyYIypinOtT8gzxC1jRVTNU3LCWdPIVsgF6a9zmiCM9CaMFoGuqUu_f_6C210GxJBGaseeThug4D24CWnydGNjmjZ2BFr0bCeKNxBhspEOM7oIFFMf5oG6wowQ8Tl54m1EeHE8T8mX9-8-ry-rq08fPq7fXlVupVeykh541_aaWQmqkYqDlSvXK6udKDdeWvVcC8nA81qwvvGF0b7TXc26fZ9T8ubgu5u7AXoH45RtNLscBpvvTLLB_KuMYWO-pu-GN4qrmheDs6NBTt9mwMkMAR3EWLqmGY1sa8Xrep-0PIAuJ8QM_m8IZ2Y_jMGtKcOY4zDlwauHX3uAH5YowOsjYNHZ6LMdXcB7jrdcsqZg4oD9CBHu_pNqLq4vhWil-AO-z6nq</recordid><startdate>199911</startdate><enddate>199911</enddate><creator>Mounsey, J Paul</creator><creator>Patel, Manoj K</creator><creator>Mistry, Dilaawar</creator><creator>John, J Edward</creator><creator>Moorman, J Randall</creator><general>Blackwell Publishing Ltd</general><general>Nature Publishing</general><scope>IQODW</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>7X8</scope><scope>5PM</scope></search><sort><creationdate>199911</creationdate><title>Protein kinase C co‐expression and the effects of halothane on rat skeletal muscle sodium channels</title><author>Mounsey, J Paul ; Patel, Manoj K ; Mistry, Dilaawar ; John, J Edward ; Moorman, J Randall</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c4846-6fe1b9d80a6e75671ea64cd7a8c3a641538d18360ef1230d5f6718fb8b20b5693</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>1999</creationdate><topic>Anesthetics, Inhalation - pharmacology</topic><topic>Anesthetics. Neuromuscular blocking agents</topic><topic>Animals</topic><topic>Biological and medical sciences</topic><topic>halothane</topic><topic>Halothane - pharmacology</topic><topic>Isoenzymes - biosynthesis</topic><topic>Kinetics</topic><topic>Medical sciences</topic><topic>Microelectrodes</topic><topic>Muscle, Skeletal - drug effects</topic><topic>Muscle, Skeletal - metabolism</topic><topic>Na channels</topic><topic>Neuropharmacology</topic><topic>Oocytes - drug effects</topic><topic>Oocytes - metabolism</topic><topic>Pharmacology. Drug treatments</topic><topic>protein kinase C</topic><topic>Protein Kinase C - biosynthesis</topic><topic>Rats</topic><topic>RNA, Messenger - biosynthesis</topic><topic>Sodium Channel Blockers</topic><topic>Sodium Channels - drug effects</topic><topic>Sodium Channels - metabolism</topic><topic>Xenopus laevis</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Mounsey, J Paul</creatorcontrib><creatorcontrib>Patel, Manoj K</creatorcontrib><creatorcontrib>Mistry, Dilaawar</creatorcontrib><creatorcontrib>John, J Edward</creatorcontrib><creatorcontrib>Moorman, J Randall</creatorcontrib><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>British journal of pharmacology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Mounsey, J Paul</au><au>Patel, Manoj K</au><au>Mistry, Dilaawar</au><au>John, J Edward</au><au>Moorman, J Randall</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Protein kinase C co‐expression and the effects of halothane on rat skeletal muscle sodium channels</atitle><jtitle>British journal of pharmacology</jtitle><addtitle>Br J Pharmacol</addtitle><date>1999-11</date><risdate>1999</risdate><volume>128</volume><issue>5</issue><spage>989</spage><epage>998</epage><pages>989-998</pages><issn>0007-1188</issn><eissn>1476-5381</eissn><coden>BJPCBM</coden><abstract>Voltage‐gated Na channels, which are potential targets for general anaesthetics, are substrates for PKC, which phosphorylates a conserved site in the channel inactivation gate. We investigated the idea that PKC modulates the effect of volatile anaesthetics on Na channels via phosphorylation of this inactivation gate site.
Na currents through rat skeletal muscle Na channel α‐subunits expressed in Xenopus oocytes were measured by two‐microelectrode voltage clamp in the presence of the volatile anaesthetic agent halothane (2‐bromo‐2‐chloro‐1,1,1‐trifluroethane). PKC activity was modulated by co‐expression of a constitutively active PKC α‐isozyme.
Halothane (0.4 mM) had no effect on Na currents. With co‐expression of PKC, however, halothane dose‐dependently enhanced the rate of Na current decay and caused a small, but statistically significant reduction in Na current amplitude.
The enhancement of Na current decay was absent in a Na channel mutant in which the inactivation gate phosphorylation site was disabled. Effects of halothane on amplitude were independent of this mutation.
Co‐expression of a PKC α‐isozyme permits an effect of halothane to hasten current decay and reduce current amplitude, at least in part through interaction with the inactivation gate phosphorylation site. We speculate that the interaction between halothane and Na channels is direct, and facilitated by PKC activity and by phosphorylation of a site in the channel inactivation gate.
British Journal of Pharmacology (1999) 128, 989–998; doi:10.1038/sj.bjp.0702877</abstract><cop>Oxford, UK</cop><pub>Blackwell Publishing Ltd</pub><pmid>10556936</pmid><doi>10.1038/sj.bjp.0702877</doi><tpages>10</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Anesthetics, Inhalation - pharmacology Anesthetics. Neuromuscular blocking agents Animals Biological and medical sciences halothane Halothane - pharmacology Isoenzymes - biosynthesis Kinetics Medical sciences Microelectrodes Muscle, Skeletal - drug effects Muscle, Skeletal - metabolism Na channels Neuropharmacology Oocytes - drug effects Oocytes - metabolism Pharmacology. Drug treatments protein kinase C Protein Kinase C - biosynthesis Rats RNA, Messenger - biosynthesis Sodium Channel Blockers Sodium Channels - drug effects Sodium Channels - metabolism Xenopus laevis |
| title | Protein kinase C co‐expression and the effects of halothane on rat skeletal muscle sodium channels |
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