g-Aminobutyric Acid Type B Receptors with Specific Heterodimer Composition and Postsynaptic Actions in Hippocampal Neurons Are Targets of Anticonvulsant Gabapentin Action

g-Aminobutyric acid (GABA) activates two qualitatively different inhibitory mechanisms through ionotropic GABAA multisubunit chloride channel receptors and metabotropic GABAB G pro-tein-coupled receptors. Evidence suggests that pharmacolog-ically distinct GABAB receptor subtypes mediate presynaptic inhibition of neurotransmitter release by reducing Ca21 con-ductance, and postsynaptic inhibition of neuronal excitability by activating inwardly rectifying K1 (Kir) conductance. How-ever, the cloning of GABAB gb1 and gb2 receptor genes and identification of the functional GABAB gb1-gb2 receptor het-erodimer have so far failed to substantiate the existence of pharmacologically distinct receptor subtypes. The anticonvul-sant, antihyperalgesic, and anxiolytic agent gabapentin (Neu-rontin) is a 3-alkylated GABA analog with an unknown mecha