Activation of Inwardly Rectifying K^+ Channel in OK Proximal Tubule Cells Involves cGMP-Dependent Phosphorylation Process

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The inwardly rectifying K<SUP>+</SUP> channel with an inward conductance of about 90 pS in the surface membrane of cultured opossum kidney proximal tubule (OKP) cell is activated by cyclic AMP-dependent protein kinase (PKA). In this study, we further exmined the involvement of the guanosine 3′, 5′-cyclic monophosphate (cGMP)-dependent process in modulation of this K<SUP>+</SUP> channel by using the patch-clamp technique. In cell-attached patches, channel activity was increased by the application of either N<SUP>2</SUP>, 2′-O-dibutyrylguanosine 3′, 5′-cyclic monophosphate (DBcGMP, 100 μM) or 8-bromoguanosine 3′, 5′-cyclic monophosphate (8BrcGMP, 100 μM), and it was inhibited by KT5823 (10 μM), a membrane-permeable specific inhibitor of cGMP-dependent protein kinase (PKG). The effect of DBcGMP on channel activity was abolished by the pretreatment of cells with KT5823 (10 μM), but it was observed in the presence of KT5720 (200 nM), a specific inhibitor of PKA. Furthermore, atrial natriuretic peptide (ANP, 10 nM) increased channel activity, which was also prevented by the application of KT5823 (10 μM). In inside-out patches, ATP (3 mM) was required to maintain channel activity, which was inhibited by KT5823 (10 μM), but it was not increased by cGMP (100 μM) alone. The channel activity was increased by the coapplication of PKG (500 U/ml) and cGMP (100 μM). These results suggest that cGMP activates the inwardly rectifying K<SUP>+</SUP> channel in OKP cells through PKG-mediated phosphorylation processes independent of PKA-mediated processes, and that ANP is an agonist which stimulates PKG-mediated processes in the proximal tubule cell. Furthermore, it is suggested that the ATP-dependent channel activity in inside-out patches is maintained at least in part by PKG, which is the membrane-bound catalytic domain.

収録刊行物

  • The Japanese journal of physiology

    The Japanese journal of physiology 48(6), 467-476, 1998-12-01

    PHYSIOLOGICAL SOCIETY OF JAPAN

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各種コード

  • NII論文ID(NAID)
    10008305910
  • NII書誌ID(NCID)
    AA00691224
  • 本文言語コード
    ENG
  • 資料種別
    ART
  • ISSN
    0021521X
  • NDL 記事登録ID
    4652928
  • NDL 雑誌分類
    ZS8(科学技術--医学--解剖学・生理学・生化学)
  • NDL 請求記号
    Z53-D40
  • データ提供元
    CJP書誌  CJP引用  NDL  J-STAGE 
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