title: ATP inhibits the hypoxia response in type I cells of rat carotid bodies.
abstract: Summary During hypoxia, ATP was released from type I (glomus) cells in the carotid bodies. We studied the action of ATP on the intracellular Ca(2+) concentration ([Ca(2+)](i)) of type I cells dissociated from rat carotid bodies using a Ca(2+) imaging technique. ATP did not affect the resting [Ca(2+)](i) but strongly suppressed the hypoxia-induced [Ca(2+)](i) elevations in type I cells. The order of purinoreceptor agonist potency in inhibiting the hypoxia response was 2-methylthioATP > ATP > ADP >> alpha, beta-methylene ATP > UTP, implicating the involvement of P2Y(1) receptors. Simultaneous measurements of membrane potential and [Ca(2+)](i) show that ATP inhibited the hypoxia-induced Ca(2+) signal by reversing the hypoxia-triggered depolarization. However, ATP did not oppose the hypoxia-mediated inhibition of the oxygen-sensitive TASK-like K(+) background current. Neither the inhibition of the large-conductance Ca(2+)-activated K(+) (maxi-K) channels nor the removal of extracellular Na(+) could affect the inhibitory action of ATP. Under normoxic condition, ATP caused hyperpolarization and increase in cell input resistance. These results suggest that the inhibitory action of ATP is mediated via the closure of background conductance(s) other than the TASK-like K(+), maxi-K or Na(+) channels. In summary, ATP exerts strong negative feedback regulation on hypoxia signaling in rat carotid type I cells.
authors.affiliation: Department of Pharmacology and Center for Neurosciences, 9-70 Medical Science Building, University of Alberta, Edmonton, Alberta, Canada T6G 2H7.
authors.forename: Jianhua
authors.initials: J
authors.lastname: Xu
authors.forename: Fenglian
authors.initials: F
authors.lastname: Xu
authors.forename: Frederick W
authors.initials: FW
authors.lastname: Tse
authors.forename: Amy
authors.initials: A
authors.lastname: Tse
mesh_terms: D000255:Adenosine Triphosphate / Q000031:analogs & derivatives / Q000378:metabolism* / Q000494:pharmacology; D000818:Animals; D002118:Calcium / Q000378:metabolism; D015220:Calcium Channels / Q000187:drug effects / Q000378:metabolism; D020013:Calcium Signaling / Q000187:drug effects / Q000502:physiology*; D002344:Carotid Body / Q000187:drug effects / Q000378:metabolism*; D025461:Feedback, Physiological / Q000187:drug effects / Q000502:physiology*; D006706:Homeostasis / Q000502:physiology*; D000860:Hypoxia / Q000378:metabolism* / Q000503:physiopathology; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D015221:Potassium Channels / Q000187:drug effects / Q000378:metabolism; D058919:Purinergic P2 Receptor Antagonists; D051381:Rats; D017207:Rats, Sprague-Dawley; D018048:Receptors, Purinergic P2 / Q000378:metabolism; D058472:Receptors, Purinergic P2Y1; D012018:Reflex / Q000187:drug effects / Q000502:physiology; D015222:Sodium Channels / Q000187:drug effects / Q000378:metabolism
chemical_list: D015220:Calcium Channels; C546384:P2ry1 protein, rat; D015221:Potassium Channels; D058919:Purinergic P2 Receptor Antagonists; D018048:Receptors, Purinergic P2; D058472:Receptors, Purinergic P2Y1; D015222:Sodium Channels; D000255:Adenosine Triphosphate; D002118:Calcium