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  • Title: The gamma-subunit governs the susceptibility of recombinant gamma-aminobutyric acid type A receptors to block by the nonimmobilizer 1,2-dichlorohexafluorocyclobutane (F6, 2N).
    Author: Zarnowska ED, Pearce RA, Saad AA, Perouansky M.
    Journal: Anesth Analg; 2005 Aug; 101(2):401-406. PubMed ID: 16037152.
    Abstract:
    UNLABELLED: To identify anesthetic effects that produce the different components of the complex anesthetic state, the so-called nonanesthetics/nonimmobilizer classes of compounds have been introduced. Because ionotropic gamma-aminobutyric acid type A (GABA(A)) receptors play an important role in the mediation of the central nervous system (CNS) effects of general anesthetics, and their susceptibility to modulation by various drugs depends on subunit composition, we have compared the effect of the nonimmobilizer 1,2-dichlorohexafluorocyclobutane (F6) on GABA(A) receptors expressed in human embryonic kidney 293 cells transfected with alpha1beta2 versus alpha1beta2gamma2s subunits. Using rapid perfusion and whole-cell recording techniques, we found that, like isoflurane, F6 blocked GABA-induced currents through alpha1beta2 receptors but, unlike isoflurane, the presence of the gamma2s subunit conferred complete resistance to block by F6. Also, in contrast to isoflurane, F6 had no effect on deactivation kinetics of GABA-induced currents in either type of receptor. We conclude that modulation of alphabetagamma receptors plays little or no role in the actions of F6, but the block of alphabeta receptors may contribute to its effects on the CNS. IMPLICATIONS: Gamma-aminobutyric acidA receptors are the target of numerous drugs affecting the central nervous system. The subunit composition of the GABAA receptors governs their interaction with many drugs. We investigated whether the gamma-subunit influences the interaction with the nonimmobilizer F6.
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