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Apical adenosine receptors are coupled with basolateral Ca++‐activated potassium channels via PLC/Ca++ signaling pathway in human airway epithelial Calu‐3 cells
Author(s) -
Wang Dong,
Sun Ying,
Yang Pingfang,
Huang Pingbo
Publication year - 2007
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.21.5.a546-b
Subject(s) - adenosine , potassium channel , secretion , microbiology and biotechnology , chemistry , adenosine receptor , medicine , apical membrane , channel blocker , purinergic signalling , receptor , ion channel , signal transduction , endocrinology , biology , biochemistry , calcium , agonist , membrane
Previous studies have demonstrated that apical extracelluar adenosine modulates anion secretion by activating CFTR via cAMP/PKA in Calu‐3 cells, a model of serous cells, a key player in liquid secretion and pathogenesis of cystic fibrosis in human airways. Adenosine receptors also couple with PLC/Ca ++ signaling, however, the role of this coupling in the anion secretion is unclear. Here, we showed that apical adenosine induced anion secretion, measured by short circuit current (Isc), was blocked by PLC inhibitors in Calu‐3 cells. In addition, the Isc was blocked by 2‐APB (a IP3 receptor blocker) and BAPTA‐AM (a Ca ++ chelator), but not by PKC inhibitors, suggesting the involvement of a PKC‐independent PLC/Ca ++ signaling. Interestingly, adenosine‐induced Isc was impaired by clotrimazole, a blocker for Ca ++ ‐activated intermediate potassium channel. Furthermore, adenosine evoked a clotrimazole‐sensitive, Ca ++ ‐dependent basolaterol K + current in apically permeabilized cells in a PLC but not PKC or PKA dependent manner. Single channel studies further revealed that adenosine activated a clostrimazole‐sensitive, Ca 2+ ‐dependent intermediate K+ channel. Our data suggest apical adenosine activates basolateral K+ channels via PLC/Ca++ and thereby increases driving force for apical anion secretion, synergizing with its modulation of CFTR via cAMP/PKA. Supported by Hong Kong RGC grant HKUST 6468/05M.