title: Adenosine stimulates depolarization and rise in cytoplasmic [Ca2+] in type I cells of rat carotid bodies.
abstract: During hypoxia, the level of adenosine in the carotid bodies increases as a result of ATP catabolism and adenosine efflux via adenosine transporters. Using Ca2+ imaging, we found that adenosine, acting via A2A receptors, triggered a rise in cytoplasmic [Ca2+] ([Ca2+]i) in type I (glomus) cells of rat carotid bodies. The adenosine response could be mimicked by forskolin (but not its inactive analog), and could be abolished by the PKA inhibitor H89. Simultaneous measurements of membrane potential (perforated patch recording) and [Ca2+]i showed that the adenosine-mediated [Ca2+]i rise was accompanied by depolarization. Ni2+, a voltage-gated Ca2+ channel (VGCC) blocker, abolished the adenosine-mediated [Ca2+]i rise. Although adenosine was reported to inhibit a 4-aminopyridine (4-AP)-sensitive K+ current, 4-AP failed to trigger any [Ca2+]i rise, or to attenuate the adenosine response. In contrast, anandamide, an inhibitor of the TWIK-related acid-sensitive K+-1 (TASK-1) channels, triggered depolarization and [Ca2+]i rise. The adenosine response was attenuated by anandamide but not by tetraethylammonium. Our results suggest that adenosine, acting via the adenylate cyclase and PKA pathways, inhibits the TASK-1 K+ channels. This leads to depolarization and activation of Ca2+ entry via VGCC. This excitatory action of adenosine on type I cells may contribute to the chemosensitivity of the carotid body during hypoxia.
authors.affiliation: Dept. of Pharmacology and Center for Neurosciences, Univ. of Alberta, Edmonton, Alberta, Canada T6G 2H7.
authors.forename: Fenglian
authors.initials: F
authors.lastname: Xu
authors.forename: Jianhua
authors.initials: J
authors.lastname: Xu
authors.forename: Frederick W
authors.initials: FW
authors.lastname: Tse
authors.forename: Amy
authors.initials: A
authors.lastname: Tse
mesh_terms: D015761:4-Aminopyridine / Q000494:pharmacology; D000241:Adenosine / Q000378:metabolism*; D058917:Adenosine A2 Receptor Antagonists; D000262:Adenylyl Cyclases / Q000378:metabolism; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002344:Carotid Body / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism; D003593:Cytoplasm / Q000187:drug effects / Q000378:metabolism*; D000860:Hypoxia / Q000503:physiopathology; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D009419:Nerve Tissue Proteins / Q000187:drug effects / Q000378:metabolism; D018408:Patch-Clamp Techniques; D026902:Potassium Channel Blockers / Q000494:pharmacology; D024683:Potassium Channels, Tandem Pore Domain / Q000187:drug effects / Q000378:metabolism; D024642:Potassium Channels, Voltage-Gated / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D043705:Receptor, Adenosine A2A / Q000378:metabolism; D019789:Tetraethylammonium / Q000494:pharmacology
chemical_list: D058917:Adenosine A2 Receptor Antagonists; D009419:Nerve Tissue Proteins; D026902:Potassium Channel Blockers; D024683:Potassium Channels, Tandem Pore Domain; D024642:Potassium Channels, Voltage-Gated; D043705:Receptor, Adenosine A2A; C420132:potassium channel subfamily K member 3; D019789:Tetraethylammonium; D015761:4-Aminopyridine; D017868:Cyclic AMP-Dependent Protein Kinases; D000262:Adenylyl Cyclases; D000241:Adenosine; D002118:Calcium