Actions of n-Alcohols on Nicotinic Acetylcholine Receptor Ion Channels in Cultured Rat Muscle Cells
The effects of the n-alcohols from pentanol to dodecanol on nAChR channel function were resolved at the single channel level. ACh-activated channel activity was recorded from isolated membrane patches using the patch clamp method. The intermediate-chain alcohols (C5-C8) had two main effects: (1) The...
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Veröffentlicht in: | Annals of the New York Academy of Sciences 1991-01, Vol.625 (1), p.365-373 |
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description | The effects of the n-alcohols from pentanol to dodecanol on nAChR channel function were resolved at the single channel level. ACh-activated channel activity was recorded from isolated membrane patches using the patch clamp method. The intermediate-chain alcohols (C5-C8) had two main effects: (1) They caused channel openings to be interrupted by brief shut or blocked periods, the duration of which was dependent on chain length of the alcohol but independent of concentration. (2) They caused a reduction in the duration of bursts of openings. The long-chain alcohols (C9-C11) produced only the second effect, and there was a decline in activity beyond undecanol. Results were consistent with a mechanism of channel blockade and were analyzed in terms of an open channel block model with a long-lived closed-blocked state beyond the blocked state. Affinity for the binding site increased with chain length up to octanol. The standard free energy per methylene group for adsorption to the site was calculated to be -3.3 kJ/mol, indicating the very hydrophobic nature of the site. |
doi_str_mv | 10.1111/j.1749-6632.1991.tb33864.x |
format | Article |
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A.</creator><creatorcontrib>MURRELL, RUTH D. ; HAYDON, D. A.</creatorcontrib><description>The effects of the n-alcohols from pentanol to dodecanol on nAChR channel function were resolved at the single channel level. ACh-activated channel activity was recorded from isolated membrane patches using the patch clamp method. The intermediate-chain alcohols (C5-C8) had two main effects: (1) They caused channel openings to be interrupted by brief shut or blocked periods, the duration of which was dependent on chain length of the alcohol but independent of concentration. (2) They caused a reduction in the duration of bursts of openings. The long-chain alcohols (C9-C11) produced only the second effect, and there was a decline in activity beyond undecanol. Results were consistent with a mechanism of channel blockade and were analyzed in terms of an open channel block model with a long-lived closed-blocked state beyond the blocked state. Affinity for the binding site increased with chain length up to octanol. The standard free energy per methylene group for adsorption to the site was calculated to be -3.3 kJ/mol, indicating the very hydrophobic nature of the site.</description><identifier>ISSN: 0077-8923</identifier><identifier>EISSN: 1749-6632</identifier><identifier>DOI: 10.1111/j.1749-6632.1991.tb33864.x</identifier><identifier>PMID: 1711811</identifier><language>eng</language><publisher>Oxford, UK: Blackwell Publishing Ltd</publisher><subject>Alcohols - pharmacology ; Animals ; Cells, Cultured ; Dose-Response Relationship, Drug ; Ion Channel Gating - drug effects ; Ion Channels - drug effects ; Ion Channels - physiology ; Kinetics ; Membrane Potentials - drug effects ; Muscles - physiology ; Rats ; Receptors, Nicotinic - drug effects ; Receptors, Nicotinic - physiology ; Structure-Activity Relationship</subject><ispartof>Annals of the New York Academy of Sciences, 1991-01, Vol.625 (1), p.365-373</ispartof><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c4085-6278275cbf9b3502519b6105603e00973997cbb375a5f285755381ae6344eb683</citedby><cites>FETCH-LOGICAL-c4085-6278275cbf9b3502519b6105603e00973997cbb375a5f285755381ae6344eb683</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1111%2Fj.1749-6632.1991.tb33864.x$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1111%2Fj.1749-6632.1991.tb33864.x$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>314,780,784,1417,27924,27925,45574,45575</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/1711811$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>MURRELL, RUTH D.</creatorcontrib><creatorcontrib>HAYDON, D. A.</creatorcontrib><title>Actions of n-Alcohols on Nicotinic Acetylcholine Receptor Ion Channels in Cultured Rat Muscle Cells</title><title>Annals of the New York Academy of Sciences</title><addtitle>Ann N Y Acad Sci</addtitle><description>The effects of the n-alcohols from pentanol to dodecanol on nAChR channel function were resolved at the single channel level. ACh-activated channel activity was recorded from isolated membrane patches using the patch clamp method. The intermediate-chain alcohols (C5-C8) had two main effects: (1) They caused channel openings to be interrupted by brief shut or blocked periods, the duration of which was dependent on chain length of the alcohol but independent of concentration. (2) They caused a reduction in the duration of bursts of openings. The long-chain alcohols (C9-C11) produced only the second effect, and there was a decline in activity beyond undecanol. Results were consistent with a mechanism of channel blockade and were analyzed in terms of an open channel block model with a long-lived closed-blocked state beyond the blocked state. Affinity for the binding site increased with chain length up to octanol. The standard free energy per methylene group for adsorption to the site was calculated to be -3.3 kJ/mol, indicating the very hydrophobic nature of the site.</description><subject>Alcohols - pharmacology</subject><subject>Animals</subject><subject>Cells, Cultured</subject><subject>Dose-Response Relationship, Drug</subject><subject>Ion Channel Gating - drug effects</subject><subject>Ion Channels - drug effects</subject><subject>Ion Channels - physiology</subject><subject>Kinetics</subject><subject>Membrane Potentials - drug effects</subject><subject>Muscles - physiology</subject><subject>Rats</subject><subject>Receptors, Nicotinic - drug effects</subject><subject>Receptors, Nicotinic - physiology</subject><subject>Structure-Activity Relationship</subject><issn>0077-8923</issn><issn>1749-6632</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1991</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqVkE1v0zAYxy3ENMrgIyBZHLgl2HH8xgVFFYxJpaCxCcHFSrwnmosbd7Ej2m-Pq1TjPF9s6__y2D-E3lJS0rzeb0oqa10IwaqSak3L1DGmRF3un6HFo_QcLQiRslC6Yi_Qyxg3hNBK1fIcnVNJqaJ0gWxjkwtDxKHHQ9F4G-6Dz7cBr50NyQ3O4sZCOnibBTcAvgYLuxRGfJVNy_t2GCAHXD5PPk0j3OHrNuGvU7Qe8BK8j6_QWd_6CK9P-wW6_fzpZvmlWH27vFo2q8LWRPFCVFJVktuu1x3jpOJUd4ISLggDQrRkWkvbdUzylveV4pJzpmgLgtU1dEKxC_Ru7t2N4WGCmMzWRZtf0A4QpmgUEbVQSmfjh9loxxDjCL3ZjW7bjgdDiTkSNhtzxGiOGM2RsDkRNvscfnOaMnVbuPsfnZFm_eOs_3UeDk9oNutfzQ8meG4o5gYXE-wfG9rxjxEyf9_8XF8avqrZby6_G83-AT9SmTc</recordid><startdate>19910101</startdate><enddate>19910101</enddate><creator>MURRELL, RUTH D.</creator><creator>HAYDON, D. A.</creator><general>Blackwell Publishing Ltd</general><scope>BSCLL</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></search><sort><creationdate>19910101</creationdate><title>Actions of n-Alcohols on Nicotinic Acetylcholine Receptor Ion Channels in Cultured Rat Muscle Cells</title><author>MURRELL, RUTH D. ; HAYDON, D. A.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c4085-6278275cbf9b3502519b6105603e00973997cbb375a5f285755381ae6344eb683</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>1991</creationdate><topic>Alcohols - pharmacology</topic><topic>Animals</topic><topic>Cells, Cultured</topic><topic>Dose-Response Relationship, Drug</topic><topic>Ion Channel Gating - drug effects</topic><topic>Ion Channels - drug effects</topic><topic>Ion Channels - physiology</topic><topic>Kinetics</topic><topic>Membrane Potentials - drug effects</topic><topic>Muscles - physiology</topic><topic>Rats</topic><topic>Receptors, Nicotinic - drug effects</topic><topic>Receptors, Nicotinic - physiology</topic><topic>Structure-Activity Relationship</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>MURRELL, RUTH D.</creatorcontrib><creatorcontrib>HAYDON, D. A.</creatorcontrib><collection>Istex</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><jtitle>Annals of the New York Academy of Sciences</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>MURRELL, RUTH D.</au><au>HAYDON, D. A.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Actions of n-Alcohols on Nicotinic Acetylcholine Receptor Ion Channels in Cultured Rat Muscle Cells</atitle><jtitle>Annals of the New York Academy of Sciences</jtitle><addtitle>Ann N Y Acad Sci</addtitle><date>1991-01-01</date><risdate>1991</risdate><volume>625</volume><issue>1</issue><spage>365</spage><epage>373</epage><pages>365-373</pages><issn>0077-8923</issn><eissn>1749-6632</eissn><abstract>The effects of the n-alcohols from pentanol to dodecanol on nAChR channel function were resolved at the single channel level. ACh-activated channel activity was recorded from isolated membrane patches using the patch clamp method. The intermediate-chain alcohols (C5-C8) had two main effects: (1) They caused channel openings to be interrupted by brief shut or blocked periods, the duration of which was dependent on chain length of the alcohol but independent of concentration. (2) They caused a reduction in the duration of bursts of openings. The long-chain alcohols (C9-C11) produced only the second effect, and there was a decline in activity beyond undecanol. Results were consistent with a mechanism of channel blockade and were analyzed in terms of an open channel block model with a long-lived closed-blocked state beyond the blocked state. Affinity for the binding site increased with chain length up to octanol. The standard free energy per methylene group for adsorption to the site was calculated to be -3.3 kJ/mol, indicating the very hydrophobic nature of the site.</abstract><cop>Oxford, UK</cop><pub>Blackwell Publishing Ltd</pub><pmid>1711811</pmid><doi>10.1111/j.1749-6632.1991.tb33864.x</doi><tpages>9</tpages></addata></record> |
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subjects | Alcohols - pharmacology Animals Cells, Cultured Dose-Response Relationship, Drug Ion Channel Gating - drug effects Ion Channels - drug effects Ion Channels - physiology Kinetics Membrane Potentials - drug effects Muscles - physiology Rats Receptors, Nicotinic - drug effects Receptors, Nicotinic - physiology Structure-Activity Relationship |
title | Actions of n-Alcohols on Nicotinic Acetylcholine Receptor Ion Channels in Cultured Rat Muscle Cells |
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