GABA Mediates Autoreceptor Feedback Inhibition in the Rat Carotid Body Via Presynaptic GABAB Receptors and TASK-1 |
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Authors: | Ian M Fearon Min Zhang Cathy Vollmer Colin A Nurse |
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Institution: | Department of Biology, McMaster University, 1280 Main Street West, Hamilton, Ontario L8S 4K1, Canada |
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Abstract: | Background K+ channels exert control over neuronal excitability by regulating resting potential and input resistance. Here, we show that GABAB 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 GABAB(1) and GABAB(2) subunits as well as endogenous GABA. The GABAB 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 μ m ), 5-aminovaleric acid (100 μ m ) and CGP 55845 (100 n m ), selective GABAB 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 Gi, or by H-89 (50 μ m ), a selective inhibitor of protein kinase A. The protein kinase C inhibitor chelerythrine chloride (100 μ m ) 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 GABAB 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. |
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