GABA mediates autoreceptor feedback inhibition in the rat carotid body via presynaptic GABAB receptors and TASK-1

Background K+ channels exert control over neuronal excitability by regulating resting potential and input resistance. Here, we show that GABA(B) receptor-mediated activation of a background K+ conductance modulates transmission at rat carotid body chemosensory synapses in vitro. Carotid body chemoreceptor (type I) cells expressed GABA(B(1)) and GABA(B(2)) subunits as well as endogenous GABA. The GABA, receptor agonist baclofen activated an anandamide- and Ba2+-sensitive TASK-1-like background K+ conductance in chemoreceptor cell clusters, but was without effect on voltage-gated Ca2+ channels. Hydroxysaclofen (50 mum), 5-aminovaleric acid (100 mum) and CGP 55845 (100 nm), selective GABA(B) receptor blockers, potentiated the hypoxia-induced receptor potential; this effect was abolished by pre-treatment with pertussis toxin (PTX; 500 ng ml(-1)), an inhibitor of G(i), or by H-89 (50 mum), a selective inhibitor of protein kinase A. The protein kinase C inhibitor chelerythrine chloride (100 mum) was without effect on this potentiation. GABAB receptor blockers also caused depolarisation of type I cells in clusters, and enhanced spike discharge in spontaneously firing cells. In functional co-cultures of type I clusters and petrosal sensory neurones, GABAB receptor blockers potentiated hypoxia-induced postsynaptic chemosensory responses mediated by the fast-acting transmitters ACh and ATP. Thus GABA(B) receptor-mediated activation of TASK-1 or a related channel provides a presynaptic autoregulatory feedback mechanism that modulates fast synaptic transmission in the rat carotid body.