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Beschreibung
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Gamma-aminobutyric acid (GABA) is the primary inhibitory neurotransmitter in the central nervous system, causing a hyperpolarization of the membrane through the opening of a Cl- channel associated with the GABAA receptor (GABAA-R) subtype. GABAA-Rs are important therapeutic targets for a range of sedative, anxiolytic, and hypnotic agents and are implicated in several diseases including epilepsy, anxiety, depression, and substance abuse. The GABAA-R is a multimeric subunit complex. To date six alphas, fourbetas and four gammas, plus alternative splicing variants of some of these subunits, have been identified (Olsen and Tobin, 1990, Whiting et al., 1999, Ogris et al., 2004). Injection in oocytes or mammalian cell lines of cRNA coding for alpha- and gamma-subunits results in the expression of functional GABAA-Rs sensitive to GABA. However, coexpression of a -subunit is required for benzodiazepine modulation. The various effects of the benzodiazepines in brain may also be mediated via different a-subunits of the receptor (McKernan et al., 2000, Mehta and Ticku, 1998, Ogris et al., 2004, P ltl et al., 2003). Anti-GABAA-Receptor, 3 -Subunit Western blot of mouse brain lysates from wild type (Control) and a3-knockout (aK/O) animals showing specific immunolabeling of the ~51k a3-subunit of the GABAA-R. The labeling was absent from a lysate prepared from a3-knockout animals.
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