Anesthetic effects on the structure and dynamics of the second transmembrane domains of nAChR alpha4beta2.

ABSTRACT: Channel functions of the neuronal alpha4beta2 nicotinic acetylcholine receptor (nAChR), one of the most widely expressed subtypes in the brain, can be inhibited by volatile anesthetics. Our Na(+) flux experiments confirmed that the second transmembrane domains (TM2) of alpha4 and beta2 in 2:3 stoichiometry, (alpha4)(2)(beta2)(3), could form pentameric channels, whereas the alpha4 TM2 alone could not. The structure, topology, and dynamics of the alpha4 TM2 and (alpha4)(2)(beta2)(3) TM2 in magnetically aligned phospholipid bicelles were investigated using solid-state NMR spectroscopy in the absence and presence of halothane and isoflurane, two clinically used volatile anesthetics. (2)H NMR demonstrated that anesthetics increased lipid conformational heterogeneity. Such anesthetic effects on

SUBMITTER: Cui T 

PROVIDER: S-EPMC2812609 | biostudies-literature | 2010 Feb

REPOSITORIES: biostudies-literature