GABA-B receptors are the metabotropic arm of GABAergic inhibition: obligate heterodimers of GABA-B1 (ligand-binding) and GABA-B2 (G-protein-coupling) subunits that signal through Gαi/o. Unlike the ionotropic GABA-A receptor (a ligand-gated Cl⁻ channel; see gaba_a_receptor_signaling), GABA-B produces slower, longer-lasting inhibition via two effector arms — presynaptic suppression of P/Q- and N-type Ca²⁺ channels that dampens neurotransmitter release (auto- and heteroreceptors), and postsynaptic activation of GIRK/Kir3 K⁺ channels that generates the slow IPSP — both reinforced by adenylate-cyclase inhibition that lowers cAMP/PKA tone. Clinically, the orthosteric agonist baclofen treats spasticity; phenibut and γ-hydroxybutyrate (sodium oxybate) are weaker/partial GABA-B agonists with additional targets. These ligands appear in gaba_a_receptor_signaling only as mechanistic contrast; this pathway is their primary home.
Organ Systems
nervous
Pathway Steps
gaba → gaba-b-receptor-activation — via orthosteric GABA binding at the GABA-B1 Venus-flytrap domain; obligate B1/B2 heterodimer, B2 couples Gαi/o. GABA-B receptors are the metabotropic arm of GABA signaling — Gi/o-coupled GPCRs (obligate heterodimers of GABA-B1 and GABA-B2), distinct from the ionotropic GABA-A channels. They mediate the slow, prolonged inhibition of GABA and are the target of baclofen, used for spasticity.
gaba-b-receptor-activation → reduced-camp — via Gαi/o → adenylate cyclase inhibition → ↓cAMP → ↓PKA tone. Via Gi/o, GABA-B activation inhibits adenylate cyclase, lowering cAMP. This reduces PKA-dependent signaling and contributes to the receptor’s modulatory, longer-lasting effects on excitability — the metabotropic counterpart to GABA-A’s fast chloride current.
gaba-b-receptor-activation → reduced-neurotransmitter-release — via Gβγ → inhibits presynaptic P/Q- and N-type Ca²⁺ channels → ↓vesicular release (auto/heteroreceptor). Presynaptically, GABA-B receptors inhibit voltage-gated Ca²⁺ channels, reducing neurotransmitter release — acting as autoreceptors (curbing GABA release) and heteroreceptors (curbing glutamate and other transmitters). This presynaptic brake is central to their tuning of synaptic transmission.
gaba-b-receptor-activation → neuronal-hyperpolarization — via Gβγ → GIRK/Kir3 K⁺ channel opening → slow IPSP → postsynaptic hyperpolarization. Postsynaptically, GABA-B receptors open GIRK potassium channels, hyperpolarizing the neuron and producing the slow inhibitory postsynaptic potential. This sustained hyperpolarization dampens excitability over a longer timescale than GABA-A — relevant to absence seizures and to baclofen’s CNS depressant effects.