title: CO2/pH chemosensory signaling in co-cultures of rat carotid body receptors and petrosal neurons: role of ATP and ACh.
abstract: The neurotransmitter mechanisms that process acid hypercapnia in the mammalian carotid body (CB) are poorly understood. Using a co-culture model containing rat CB chemoreceptor (type 1 cell) clusters and petrosal neurons (PN), we tested the hypothesis that co-released ACh and ATP was an important mechanism. Sensory transmission from type I clusters to PN in co-culture occurred at chemical synapses via co-release of ATP and ACh because isohydric hypercapnia depolarized and/or increased firing in co-cultured PN, but not in PN cultured alone; PN chemoexcitatory responses were inhibited by decreasing the extracellular Ca(2+):Mg2+ ratio; partial inhibition of these responses occurred during separate perfusion of cholinergic (hexamethonium or mecamylamine) and P2X (suramin) receptor blockers, although inhibition was often complete with both blockers present; and rapid chemoexcitatory responses to hypercapnia were inhibited by acetazolamide (10 microM), an inhibitor of carbonic anhydrase, localized in type I cells. Acidosis (pH = 7.0, 7.2) enhanced the ATP-induced whole cell current in functional PN relative to that at physiologic pH (7.4), suggesting that increased sensitivity of postsynaptic P2X receptors may contribute to acid chemotransmission. Type I cells in CB tissue sections expressed vesicular acetylcholine transporter (VAChT), a cholinergic marker, as revealed by confocal immunofluorescence. Thus co-release of ACh and ATP is an important neurotransmitter mechanism for processing isohydric and acidic hypercapnia in the rat carotid body.
authors.affiliation: Department of Biology, McMaster University, Hamilton, Ontario L8S 4K1, Canada.
authors.forename: Min
authors.initials: M
authors.lastname: Zhang
authors.forename: Colin A
authors.initials: CA
authors.lastname: Nurse
mesh_terms: D000109:Acetylcholine / Q000378:metabolism*; D000143:Acids / Q000378:metabolism; D000200:Action Potentials / Q000502:physiology; D000255:Adenosine Triphosphate / Q000378:metabolism*; D000818:Animals; D002245:Carbon Dioxide / Q000378:metabolism; D002256:Carbonic Anhydrases / Q000378:metabolism; D002344:Carotid Body / Q000502:physiology*; D002478:Cells, Cultured; D002628:Chemoreceptor Cells / Q000378:metabolism*; D017950:Ganglia, Sensory / Q000166:cytology / Q000378:metabolism; D006863:Hydrogen-Ion Concentration; D006935:Hypercapnia / Q000378:metabolism / Q000503:physiopathology; D026901:Membrane Transport Proteins / Q000378:metabolism; D009475:Neurons, Afferent / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D018048:Receptors, Purinergic P2 / Q000502:physiology; D015398:Signal Transduction / Q000502:physiology*; D009435:Synaptic Transmission / Q000502:physiology; D050494:Vesicular Acetylcholine Transport Proteins
chemical_list: D000143:Acids; D026901:Membrane Transport Proteins; D018048:Receptors, Purinergic P2; C493461:Slc18a3 protein, rat; D050494:Vesicular Acetylcholine Transport Proteins; D002245:Carbon Dioxide; D000255:Adenosine Triphosphate; D002256:Carbonic Anhydrases; D000109:Acetylcholine