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
Hauptverfasser: MURRELL, RUTH D., HAYDON, D. A.
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creator MURRELL, RUTH D.
HAYDON, D. A.
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
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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. 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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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