The effect of general anesthetics on the dynamics of phosphatidylcholine-acetylcholine receptor interactions in reconstituted vesicles.
The interaction of general anesthetics at the lipid/protein interface of the nicotinic acetylcholine receptor reconstituted in dioleoylphosphatidylcholine bilayers at various lipid/protein ratios has been studied using the electron spin resonance spectra of phosphatidylcholine spin-labeled at the fourteenth acyl carbon (14-PCSL). In addition to the bilayer spectrum, the spin label reported a more motionally restricted environment whose contribution increased with increasing protein/lipid ratio. Exchange between these two environments occurred at a rate of approx. 6 x 10(7) s-1. The motionally restricted, protein-associated 14-PCSL had a rotational correlation time of about 10-20 ns, an order of magnitude slower than when in the bilayer. Addition of 1-hexanol (up to 16 mM) to the reconstituted receptor perturbed the acyl chains of the bulk lipid phase, but the motional properties of the lipid acyl chains at the protein/lipid interface near the membrane center were not significantly perturbed on the EPR motional time-scale. Similarly, anesthetics that were less effective at perturbing the bilayer, such as pentobarbital (up to 2 mM) and isoflurane (7 mM), did not perturb the lipid/protein interface on the conventional EPR motional time scale.
Abadji
V C
VC
Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA.
Raines
D E
DE
Watts
A
A
Miller
K W
KW
D000768:Anesthesia, General; D000777:Anesthetics / Q000494:pharmacology*; D000818:Animals; D000441:Hexanols / Q000494:pharmacology; D008051:Lipid Bilayers / Q000378:metabolism*; D010713:Phosphatidylcholines / Q000378:metabolism*; D011978:Receptors, Nicotinic / Q000737:chemistry / Q000187:drug effects* / Q000378:metabolism; D014101:Torpedo
D000777:Anesthetics; D000441:Hexanols; D008051:Lipid Bilayers; D010713:Phosphatidylcholines; D011978:Receptors, Nicotinic; C036260:1-hexanol; C017251:1,2-oleoylphosphatidylcholine