Postsynaptic action of GABA in modulating sensory transmission in co‐cultures of rat carotid body via GABAA receptors
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abstract
GABA is expressed in carotid body (CB) chemoreceptor type I cells and has previously been reported to modulate sensory transmission via presynaptic GABAB receptors. Because low doses of clinically important GABAA receptor (GABAAR) agonists, e.g. benzodiazepines, have been reported to depress afferent CB responses to hypoxia, we investigated the potential contribution of GABAAR 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 GABAA 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 EC50 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 GABAAR 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 GABAAR β subunit. These data suggest that GABA, released from the CB during hypoxia, inhibits sensory discharge postsynaptically via a shunting mechanism involving GABAA receptors.
