GABA_B receptors

γ-Aminobutyric acid (GABA) is the major inhibitory neurotransmitter in the CNS and has a key role in modulating neuronal activity. GABA mediates its action via 2 classes of receptors, ionotropic GABA_A and GABA_C and metabotropic GABA_B receptors. Unlike GABA_A and _C receptors, which form chloride channels and are involved in fast synaptic inhibition, GABA_B receptors are guanine nucleotide-binding (G) protein-coupled receptors that modulate calcium (Ca²⁺) and potassium (K⁺) channels and elicit both presynaptic and slow postsynaptic inhibition. GABA_B receptors are broadly expressed in the nervous system, modulating synaptic excitability and plasticity in the cerebral cortex, generating rhythmic activity in cortical and thalamic circuits, relaying primary afferent input to the spinal cord and brainstem, and affecting the activity of dopaminergic and other monoaminergic neurons. These receptors have been implicated in a wide variety of neurologic and psychiatric disorders, including absence seizures, γ-hydroxybutyrate toxicity, and, more recently, autoimmune limbic encephalitis. Baclofen is the only clinically available GABA_B receptor agonist and is utilized for treatment of spasticity, dystonia, and some types of neuropathic pain. GABA_B receptors may also provide a target for management of drug addiction, anxiety, and visceral pain. The structure, functions, and clinical implications of GABA_B receptors have been extensively reviewed^1,–,7