GABA is expressed in carotid body (CB) chemoreceptor type I cells and has previously been reported to modulate sensory transmission via presynaptic GABA B receptors. Because low doses of clinically important GABA A receptor (GABA A R) agonists, e.g. benzodiazepines, have been reported to depress afferent CB responses to hypoxia, we investigated the potential contribution of GABA A R in co-cultures of rat type I cells and sensory petrosal neurones (PNs). During gramicidin perforated-patch recordings (to preserve intracellular Cl − ), GABA and/or the GABA A agonist muscimol (50 μm) induced a bicuculline-sensitive membrane depolarization in isolated PNs. GABA-induced whole-cell currents reversed at ∼ −38 mV and had an EC 50 of ∼10 μm (Hill coefficient = ∼1) at −60 mV. During simultaneous PN and type I cell recordings at functional chemosensory units in co-culture, bicuculline reversibly potentiated the PN, but not type I cell, depolarizing response to hypoxia. Application of the CB excitatory neurotransmitter ATP (1 μm) over the soma of functional PN induced a spike discharge that was markedly suppressed during co-application with GABA (2 μm), even though GABA alone was excitatory. RT-PCR analysis detected expression of GABAergic markers including mRNA for α1, α2, β2, γ2S, γ2L and γ3 GABA A R subunits in petrosal ganglia extracts. Also, CB extracts contained mRNAs for GABA biosynthetic markers, i.e. glutamate decarboxylase (GAD) isoforms GAD 67A,E, and GABA transporter isoforms GAT 2,3 and BGT-1. In CB sections, sensory nerve endings apposed to type I cells were immunopositive for the GABA A R β subunit. These data suggest that GABA, released from the CB during hypoxia, inhibits sensory discharge postsynaptically via a shunting mechanism involving GABA A receptors.

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