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) 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.
Murrell
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RD
Physiological Laboratory, University of Cambridge, England.
Haydon
D A
DA
D000438:Alcohols / Q000494:pharmacology*; D000818:Animals; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D015640:Ion Channel Gating / Q000187:drug effects; D007473:Ion Channels / Q000187:drug effects / Q000502:physiology*; D007700:Kinetics; D008564:Membrane Potentials / Q000187:drug effects; D009132:Muscles / Q000502:physiology*; D051381:Rats; D011978:Receptors, Nicotinic / Q000187:drug effects / Q000502:physiology*; D013329:Structure-Activity Relationship
D000438:Alcohols; D007473:Ion Channels; D011978:Receptors, Nicotinic