Potassium channels underlie postsynaptic but not presynaptic GABAB receptor-mediated inhibition on ventrolateral periaqueductal gray neurons

γ-Aminobutyric acid (GABA) is the principle inhibitory neurotransmitter in adult mammalian brain. GABA receptors B subtype (GABABRs) are abundantly expressed at presynaptic and postsynaptic neuronal structures in the rat ventrolateral periaqueductal gray (PAG), an area related to pain regulation. Activation of GABABRs by baclofen, a selective agonist, induces presynaptic inhibition by decreasing presynaptic glutamate release. At the same time, baclofen induces a postsynaptic inhibitory membrane current or potential. We here report that in the ventrolateral PAG, the postsynaptic inhibition is mediated by activation of G protein-coupled inwardly rectifying K+ (GIRK) channels. Blockade of K+ channels largely prevents postsynaptic action of baclofen. In contrast, presynaptic inhibition of baclofen is insensitive to K+ channel blockade. The data indicate that potassium channels play different roles in GABABR-mediated presynaptic and postsynaptic inhibition on PAG neurons.

► Baclofen (a GABABR agonist) action on PAG neurons investigated.
► Postsynaptically, baclofen inhibits PAG neurons by activating K+ conductances.
► Presynaptically, baclofen inhibits glutamate release by a way other than K+ conductances.
► The data indicate GABABR-mediated pre- and postsynaptic inhibition is different.