ATP inhibits the hypoxia response in type I cells of rat carotid bodies

Jianhua Xu, Fenglian Xu, Frederick W. Tse, Amy Tse

Research output: Contribution to journalArticle

35 Citations (Scopus)

Abstract

During hypoxia, ATP was released from type I (glomus) cells in the carotid bodies. We studied the action of ATP on the intracellular Ca2+ concentration ([Ca2+]i) of type I cells dissociated from rat carotid bodies using a Ca2+ imaging technique. ATP did not affect the resting [Ca2+]i but strongly suppressed the hypoxia-induced [Ca2+]i elevations in type I cells. The order of purinoreceptor agonist potency in inhibiting the hypoxia response was 2-methylthioATP > ATP > ADP ≫ α, β-methylene ATP > UTP, implicating the involvement of P2Y1 receptors. Simultaneous measurements of membrane potential and [Ca2+]i show that ATP inhibited the hypoxia-induced Ca2+ 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.

Original languageEnglish (US)
Pages (from-to)1419-1430
Number of pages12
JournalJournal of Neurochemistry
Volume92
Issue number6
DOIs
StatePublished - Mar 1 2005

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Carotid Body
Rats
Adenosine Triphosphate
Cells
Hypoxia
Purinergic P2Y1 Receptors
Large-Conductance Calcium-Activated Potassium Channels
Uridine Triphosphate
Depolarization
Membrane Potentials
Adenosine Diphosphate

Keywords

  • Autofeedback regulation
  • Carotid body
  • Oxygen sensing
  • P2y purinoreceptor

ASJC Scopus subject areas

  • Biochemistry
  • Cellular and Molecular Neuroscience

Cite this

ATP inhibits the hypoxia response in type I cells of rat carotid bodies. / Xu, Jianhua; Xu, Fenglian; Tse, Frederick W.; Tse, Amy.

In: Journal of Neurochemistry, Vol. 92, No. 6, 01.03.2005, p. 1419-1430.

Research output: Contribution to journalArticle

Xu, Jianhua ; Xu, Fenglian ; Tse, Frederick W. ; Tse, Amy. / ATP inhibits the hypoxia response in type I cells of rat carotid bodies. In: Journal of Neurochemistry. 2005 ; Vol. 92, No. 6. pp. 1419-1430.
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