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Triarylmethane‐34 (TRAM‐34), inhibitor of Ca 2+ ‐activated K + channels of intermediate conductance, is a potent blocker of gap junctions
Author(s) -
Figueroa Xavier F,
Gaete Pablo S,
Sáez Juan C,
Riquelme Manuel
Publication year - 2010
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.24.1_supplement.lb542
Subject(s) - gap junction , lucifer yellow , connexin , chemistry , biophysics , intracellular , hela , biochemistry , cell , biology
Ca 2+ ‐activated K + channels of intermediate conductance (IK Ca ) and gap junctions (GJs) between endothelial and smooth muscle cells have been proposed to play a central role in the vasodilator response mediated by the endothelium‐derived hyperpolarizing factor (EDHF). Although TRAM‐34, the IK Ca channels blocker, has emerged as an important pharmacological tool for studying EDHF‐mediated responses, its effect on GJs has not been described. We analyzed intercellular communication and cellular distribution of the GJ protein subunit, connexins (Cxs), in HeLa cells transfected with Cx43 or Cx43 conjugated to EGFP. Treatment with 10μM TRAM‐34 induced a time dependent reduction in dye coupling to Lucifer yellow; the average number of coupled cells observed in positive tests was reduced by ~50% after 20 min and abolished after 70 min. Dye coupling was recovered to control 30 min after TRAM‐34 wash out. The reduction in GJ communication was not associated with changes in levels or distribution of Cx43‐EGFP. Therefore, TRAM‐34, in addition to inhibit IK Ca channels, also potently blocks the cell‐to‐cell communication mediated by the GJ protein Cx43 that is an important connexin involved in the coordination of resistance vessel function. VRAID 15/2009, FONDEF D07I1086.