Role of cyclic ADP-Ribose in ATP-activated potassium currents in alveolar macrophages

Satoru Ebihara, Tsukasa Sasaki, Wataru Hida, Yoshihiro Kikuchi, Takako Oshiro, Sanae Shimura, Shin Takasawa, Hiroshi Okamoto, Akinori Nishiyama, Norio Akaike, Kunio Shirato

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Abstract

There is growing evidence that extracellular ATP causes a dramatic change in the membrane conductance of a variety of inflammatory cells. In the present study, using the nystatin perforated patch recording configuration, we found that ATP (0.3-30 μM) induced a transient outward current in a concentration-dependent manner and that the reversal potential of the ATP- induced outward current was close to the K+ equilibrium potential, indicating that the membrane behaves like a K+ electrode in the presence of ATP. The first application of ATP to alveolar macrophages perfused with Ca2+-free external solution could induce the outward current, but the response to ATP was diminished with successive applications. Intracellular perfusion with a Ca2+ chelator, 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'- tetraacetic acid, also diminished the response. When cyclic ADP-ribose (cADPR) was applied to the macrophage cytoplasm, a transient outward current was elicited. Thereafter, the successive outward current was inhibited, suggesting the involvement of cADPR in the response. Intracellular perfusion with inositol 1,4,5-trisphosphate also induced a transient outward current, but the successive current was not inhibited. The ATP-induced outward current was abolished when 8-amino-cADPR (as a blocker of cADPR, 10-6-10-5 M) was introduced into the cytoplasm. Homogenates of alveolar macrophages showed both ADP-ribosyl cyclase and cADPR hydrolase activities, and CD38 (ADP- ribosyl cyclase/cADPR hydrolase) expression was confirmed by reverse transcriptase-polymerase chain reaction and Western blot analyses. These results indicate that ATP activates K+ currents by releasing Ca2+ from cADPR-sensitive internal Ca2+ stores.

Original languageEnglish
Pages (from-to)16023-16029
Number of pages7
JournalJournal of Biological Chemistry
Volume272
Issue number25
DOIs
Publication statusPublished - 1997 Jun 20

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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    Ebihara, S., Sasaki, T., Hida, W., Kikuchi, Y., Oshiro, T., Shimura, S., Takasawa, S., Okamoto, H., Nishiyama, A., Akaike, N., & Shirato, K. (1997). Role of cyclic ADP-Ribose in ATP-activated potassium currents in alveolar macrophages. Journal of Biological Chemistry, 272(25), 16023-16029. https://doi.org/10.1074/jbc.272.25.16023