Y Blednov | PubMed Health

PubMed2001

Alcohol actions on GABA(A) receptors: from protein structure to mouse behavior.

This article represents the proceedings of a symposium at the 2000 ISBRA Meeting in Yokohama, Japan. The chairs were R. Adron Harris and Susumu Ueno. The presentations were (1) Protein kinase Cepsilon-regulated sensitivity of gamma-aminobutyric acid type A (GABAA) receptors to allosteric agonists, by Robert O. Messing, A. M. Sanchez-Perez, C. W. Hodge, T. McMahon, D. Wang, K. K. Mehmert, S. P. Kelley, A. Haywood, and M. F. Olive; (2) Genetic and functional analysis of a GABAA receptor gamma2 subunit variant: A candidate for quantitative trait loci involved in alcohol sensitivity and withdrawal, by Kari J. Buck and Heather M. Hood; (3) Tryptophan-scanning mutagenesis in GABAA receptor subunits: Channel gating and alcohol actions, by Susumu Ueno; and (4) Can a single binding site account for actions of alcohols on GABAA and glycine receptors? by R. Adron Harris, Yuri Blednov, Geoffrey Findlay, and Maria Paola Mascia.

Amino Acid Sequence↗

PubMed1996

Propofol produces differences in behavior but not chloride channel function between selected lines of mice.

We report differential central nervous system (CNS) sensitivity to propofol between Long Sleep (LS) and Short Sleep (SS) mice, selectively bred for their differential CNS sensitivity to ethanol. Intravenous propofol requirements for loss of righting reflex, or sleep time, were measured to define the extent of this sensitivity. LS mice slept approximately two times longer than SS mice at equal doses. Awakening plasma and brain levels of the SS line were, respectively, two and three times that of the LS line (P < 0.0001). This suggests that the LS and SS sleep time difference is CNS mediated, and that propofol and ethanol may share common genes that determine anesthetic sensitivities. The ethanol effect may be at least partially mediated by gamma-aminobutyric acid-A (GABAA) receptor function. Propofol had no differential effect on GABAA receptor function, as measured by chloride flux in LS and SS brain microsac preparations. Either the GABAA receptor does not mediate propofol sleep time, or qualitative differences cannot be demonstrated using 36Cl- uptake in brain membranes.

Anesthetics, Intravenous↗