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Influence of the state of shosphorylation on the interaction of anthracene‐9‐carboxylic acid with Ca2+‐activated Cl‐ channels in pulmonary artery myocytes
Author(s) -
Wiwchar Michael,
Huebner Marissa,
Greenwood Ian A.,
Leblanc Normand
Publication year - 2009
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.23.1_supplement.579.10
Subject(s) - niflumic acid , chemistry , phosphorylation , chloride channel , biophysics , biochemistry , biology
Ca 2+ ‐dependent Cl − currents (I ClCa ) are down regulated by phosphorylation in arterial smooth muscle cells. We recently showed that niflumic acid (NFA), an inhibitor of I ClCa , is less efficacious at blocking the current in conditions promoting phosphorylation. This study aimed to assess whether another Cl − channel blocker, anthracene‐9‐carboxylic acid (A9C), is also affected by channel phosphorylation. A9C blocks I ClCa at positive potentials but paradoxically stimulates the inward I ClCa tail after repolarization to negative potentials. I ClCa was evoked by pipette solutions containing 500 nM free Ca 2+ with or without 5 mM ATP to alter the state of phosphorylation. A9C (10‐500 μM) produced voltage‐dependent block of I ClCa that was more potent in cells dialyzed with ATP vs. 0 ATP. A9C enhanced I ClCa tail at ‐80 mV by causing a large negative shift in voltage‐dependence in both cell groups. Finally, phosphorylation greatly attenuated the rate of recovery of I ClCa at +80 mV upon washout of A9C, but not I ClCa tail at ‐80 mV. As for NFA, the complex actions of A9C with I ClCa are profoundly influenced by the state of channel phosphorylation and we propose the existence of multiple binding sites for A9C.