Lipid effects on nicotinic acetylcholine receptor gating and kinetics: a structural-functional correlation.
The nicotinic acetylcholine receptor (AChR) is still the paradigm of rapid ligand-gated ion channels. Since the early finding of a motionally restricted shell of lipids ("annulus") in the immediate perimeter of the membrane-bound AChR, experimental evidence has supported the notion that the interface between the protein moiety and the adjacent lipid molecules is the site of action of a variety of pharmacologically relevant substances, including non-competitive inhibitors of the cholinergic system like some local anesthetics, short-chain alcohols, and steroids. Patch-clamp data on cells expressing the AChR protein add another dimension to this knowledge, enabling correlations to be established between the chemical composition of lipid-modified cells and the functional properties (ligand binding, channel gating) of the receptor protein in situ.
Barrantes
F J
FJ
Instituto de Investigaciones Bioquímicas, CONICET, Bahía Blanca, Argentina.
D000777:Anesthetics / Q000494:pharmacology; D000818:Animals; D002784:Cholesterol / Q000378:metabolism / Q000494:pharmacology; D003907:Dexamethasone / Q000494:pharmacology; D004578:Electron Spin Resonance Spectroscopy; D005230:Fatty Acids, Nonesterified / Q000378:metabolism / Q000494:pharmacology; D015640:Ion Channel Gating / Q000187:drug effects; D007700:Kinetics; D008563:Membrane Lipids / Q000378:metabolism* / Q000494:pharmacology; D011978:Receptors, Nicotinic / Q000187:drug effects / Q000378:metabolism*; D013329:Structure-Activity Relationship; D014101:Torpedo
D000777:Anesthetics; D005230:Fatty Acids, Nonesterified; D008563:Membrane Lipids; D011978:Receptors, Nicotinic; D003907:Dexamethasone; D002784:Cholesterol