Actions of n‐alcohols on nicotinic acetylcholine receptor channels in cultured rat myotubes.

Abstract

SUMMARY1. The actions of the n-alcohols from pentanol to dodecanol on nicotinic acetylcholine receptor (nAChR) channels were investigated by recording single AChactivated channel activity from inside-out membrane patches isolated from cultured rat myotubes. Alcohols were applied to the cytoplasmic side of the membrane; aqueous concentrations ranged from 11 7 mM-pentanol to 0-02 mm-dodecanol.2. The intermediate-chain alcohols (pentanol to octanol) caused channel currents to fluctuate between the fully open and closed state level so that openings occurred in bursts interrupted by brief gaps. Closed time distributions were fitted well with two exponential components, the fast component representing the closures within a burst. The number of gaps within a burst was dependent on alcohol concentration whereas gap duration was independent of concentration but increased with increasing chain length of the alcohol up to octanol.3. Nonanol and decanol reduced the mean duration of bursts of openings but did not cause an increase in the number of short closed intervals within a burst. Beyond decanol there was a decline in the ability of the n-alcohols to affect channel function. A saturated solution of undecanol (0-07 mM) reduced the mean open time by 33+17 %, whereas a saturated solution of dodecanol had no significant effect. Over the range of concentrations tested this describes the effects of all the n-alcohols (C5 to C12) on channel gating reasonably well.6. Blocking rate constants (k+B) for pentanol through to nonanol were calculated to be between 2 8 and 5-7 x 106 M-1 s-1. These values are based on the assumption that the concentration of the alcohols at their site(s) of action was equal to the aqueous concentration applied to the membrane.

Involvement of connexin 43 in human trophoblast cell fusion and differentiation

“…Nevertheless, heptanol have been implicated in other biological processes. For example, it could modulate the activity of nicotinic acetylcholine receptor channels in cultured rat myotubes (Murrell et al, 1991) and the Ca 2+ -activated K + channel expressed in Xenopus oocyte (Chu and Treistman, 1997). Furthermore, heptanol and octanol were thought to affect some of the initiating responses of intracellular calcium elevation (Venance et al, 1998).…”

Confirmation of quantitative trait loci for ethanol sensitivity in long-sleep and short-sleep mice.

“…One explanation could be that the Acrd and Acrg genes, which are in the candidate region for Lore1 and code for the acetylcholine receptor subunits delta and gamma, respectively, are not expressed in the CNS but in the peripheral nervous system. Instead, Lore1 may mediate the righting response, in part via peripheral motor control; such nicotinic receptors have been shown to be sensitive to alcohol (Gage et al 1975;Aiken et al 1991;Murrell et al 1991).…”

Alteration of the L‐type calcium current in guinea‐pig single ventricular myocytes by heptaminol hydrochloride

“…Whatever the pathway followed, these agents are known to disturb the membrane bilayers lipid and protein composition and/or conformation as a result of an interaction with membrane lipids and/or membrane proteins (see Tas et al, 1990;Murrell et al, 1991). The effects of heptaminol on ICa amplitude described in this work are qualitatively similar to those reported by others for general and local anaesthetics in various tissues including cardiac muscle cells (Ikemoto et al, 1985;Hirota et al, 1988;Sanchez-Chapula, 1988;Terrar & Victory, 1988;Murrell et al, 1991). As discussed by Mongo & Vassort (1990) for the effects of straight chain alcohols and halogenated compounds, the decrease in peak ICa by heptaminol may result from changes in the membrane calcium channel activity as a consequence of: (1) an interaction of heptaminol molecule with membrane lipids and/or proteins, and (2) its alteration of intracellular free calcium ion concen-tration.…”

“…Although, the molecular basis of the action of membrane active substances is not well understood, it is generally admitted that two pathways, one hydrophobic the other hydrophilic, are used by these compounds to reach their site of action and this depends on the fact that molecules are or not amphiphile. The hydrophobic pathway can use the hydrophobic pockets on sensitive proteins as targets (Richards et al, 1978;Franks & Lieb, 1987;Tas et al, 1990;Murrell et al, 1991) and/or lipophilic regions of the membrane (Seeman, 1972;Haydon & Urbam 1983a,b). Whatever the pathway followed, these agents are known to disturb the membrane bilayers lipid and protein composition and/or conformation as a result of an interaction with membrane lipids and/or membrane proteins (see Tas et al, 1990;Murrell et al, 1991).…”

“…The hydrophobic pathway can use the hydrophobic pockets on sensitive proteins as targets (Richards et al, 1978;Franks & Lieb, 1987;Tas et al, 1990;Murrell et al, 1991) and/or lipophilic regions of the membrane (Seeman, 1972;Haydon & Urbam 1983a,b). Whatever the pathway followed, these agents are known to disturb the membrane bilayers lipid and protein composition and/or conformation as a result of an interaction with membrane lipids and/or membrane proteins (see Tas et al, 1990;Murrell et al, 1991). The effects of heptaminol on ICa amplitude described in this work are qualitatively similar to those reported by others for general and local anaesthetics in various tissues including cardiac muscle cells (Ikemoto et al, 1985;Hirota et al, 1988;Sanchez-Chapula, 1988;Terrar & Victory, 1988;Murrell et al, 1991).…”