title: Postsynaptic action of GABA in modulating sensory transmission in co-cultures of rat carotid body via GABA(A) receptors.
abstract: 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 microm) induced a bicuculline-sensitive membrane depolarization in isolated PNs. GABA-induced whole-cell currents reversed at approximately -38 mV and had an EC50 of approximately 10 microm (Hill coefficient = approximately 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 microm) over the soma of functional PN induced a spike discharge that was markedly suppressed during co-application with GABA (2 microm), even though GABA alone was excitatory. RT-PCR analysis detected expression of GABAergic markers including mRNA for alpha1, alpha2, beta2, gamma2S, gamma2L and gamma3 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 beta subunit. These data suggest that GABA, released from the CB during hypoxia, inhibits sensory discharge postsynaptically via a shunting mechanism involving GABA(A) receptors.
authors.affiliation: Department of Biology, McMaster University, Hamilton, Ontario, Canada.
authors.forename: Min
authors.initials: M
authors.lastname: Zhang
authors.forename: Katherine
authors.initials: K
authors.lastname: Clarke
authors.forename: Huijun
authors.initials: H
authors.lastname: Zhong
authors.forename: Cathy
authors.initials: C
authors.lastname: Vollmer
authors.forename: Colin A
authors.initials: CA
authors.lastname: Nurse
mesh_terms: D000200:Action Potentials / Q000187:drug effects / Q000502:physiology; D000255:Adenosine Triphosphate / Q000494:pharmacology; D000818:Animals; D002344:Carotid Body / Q000166:cytology* / Q000378:metabolism; D015687:Cell Hypoxia / Q000502:physiology; D002478:Cells, Cultured; D002628:Chemoreceptor Cells / Q000187:drug effects / Q000502:physiology*; D018920:Coculture Techniques; D004305:Dose-Response Relationship, Drug; D018755:GABA Agonists / Q000494:pharmacology; D018756:GABA Antagonists / Q000494:pharmacology; D050485:GABA Plasma Membrane Transport Proteins / Q000235:genetics; D058785:GABA-A Receptor Agonists; D058787:GABA-A Receptor Antagonists; D058786:GABA-B Receptor Agonists; D058788:GABA-B Receptor Antagonists; D005724:Ganglia / Q000166:cytology / Q000378:metabolism; D015870:Gene Expression / Q000187:drug effects; D005968:Glutamate Decarboxylase / Q000235:genetics; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D009411:Nerve Endings / Q000187:drug effects / Q000378:metabolism; D009475:Neurons, Afferent / Q000187:drug effects / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D011963:Receptors, GABA-A / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D018080:Receptors, GABA-B / Q000502:physiology; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology*; D005680:gamma-Aminobutyric Acid / Q000494:pharmacology / Q000502:physiology*
chemical_list: D018755:GABA Agonists; D018756:GABA Antagonists; D050485:GABA Plasma Membrane Transport Proteins; D058785:GABA-A Receptor Agonists; D058787:GABA-A Receptor Antagonists; D058786:GABA-B Receptor Agonists; D058788:GABA-B Receptor Antagonists; C502185:Gabrb2 protein, rat; D011963:Receptors, GABA-A; D018080:Receptors, GABA-B; D005680:gamma-Aminobutyric Acid; D000255:Adenosine Triphosphate; D005968:Glutamate Decarboxylase