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Evidence for direct stimulation by estrogen receptor agonists (diarylpropionitrile and propylpyrazole‐triol) of the large‐conductance Ca 2+ ‐activated K + channel in human cardiac fibroblasts
Author(s) -
Wang YaJean,
Lin MingWei,
Wu ShengNan,
Sung Ruey J
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.21.6.a957-a
Subject(s) - gating , chemistry , intracellular , biophysics , conductance , stimulation , depolarization , estrogen receptor , ion channel , membrane potential , receptor , endocrinology , medicine , biochemistry , biology , mathematics , combinatorics , cancer , breast cancer
The agonists selective for estrogen receptor (ER)‐ α propylpyrazole‐triol, PPT) and ER‐β diarylpropionitrile, DPN) can bind to the ER‐α and ER‐β receptors which may be localized to the plasma membrane. It is unclear whether DPN or PPT influence ion channels linked to non‐genomic mechanism. We tested the hypothesis that DPN or PPT directly stimulates the large‐conductance Ca 2+ ‐activated K + (BK Ca ) channels in human cardiac fibroblasts (HCFs). In whole‐cell configuration, depolarizing pulses evoked K + outward currents in an outward rectification in HCFs, the amplitude of which was increased by DPN or PPT. Applied to the intracellular surface of excised patches, PPT or DPN enhanced BK Ca ‐channel activity with no change in single‐channel conductance. DPN and PPT increased BK Ca ‐channel activity with an EC 50 value of 2.3 and 2.6 μM, respectively. The mean closed time of these channels measured during the exposure to DPN or PPT was reduced with no change in the gating charge of the channels. Intracellular Ca 2+ was not altered in the presence of these two compounds. RT‐PCR study also revealed that no change in the transcriptional level of the BK Ca channel α‐subunit was observed in treatment with DPN or PPT. Our data suggest that PPT‐ and DPN‐mediated activation of BK Ca channels reveal novel pharmacological properties attributable to the activity of these channels.