Modulation of nicotinic acetylcholine receptor single-channel behavior upon modification of membrane cholesterol

GARBUS INGRID,; MICHAEL WHITE,; BARRANTES FRANCISCO,

Bariloche

Congreso; Argentine Society for Biochemistry and Molecular Biology XXXIX Annual Meeting (SAIB) and Biophysical Society of Argentina XXXII Annual Meeting; 2003

Argentine Society for Biochemistry and Molecular Biology (SAIB) and Biophysical Society of Argentina

The ability of the nicotinic acetylcholine receptor (achr) to conductcations across the membrane and undergo conformational changesis highly dependent on the presence of cholesterol (chol). Westudied the effect of membrane chol enrichment or depletion onsingle-channel kinetics of adult muscle-type achr in cho-k1/a5 cellstreated with methyl- β-cyclodextrin (cdx) and chol-cdx,respectively. Chol depletion caused a lengthening of the achrchannel mean open time, whereas its enrichment diminished thiskinetic parameter. These changes were accompanied by significantchanges in the open probability of the channel, whereas the burstduration and the number of events per burst remained unchanged.No modifications of channel amplitude were observed. Underhyperpolarizing conditions, the effect of chol depletion was nolonger observed. A plausible explanation of these results is thatregulation is exerted on endogenous chol at specific sitespresumably located at the achr-lipid interface.