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The role of large conductance voltage‐ and Ca 2+ ‐activated K + channels as low affinity receptors for 17β‐estradiol in guinea pig urinary bladder smooth muscle excitability
Author(s) -
Provence Aaron,
Hristov Kiril,
Parajuli Shankar,
Petkov Georgi
Publication year - 2015
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.29.1_supplement.845.8
Subject(s) - bk channel , hyperpolarization (physics) , membrane potential , chemistry , depolarization , biophysics , patch clamp , endocrinology , medicine , receptor , biology , biochemistry , stereochemistry , nuclear magnetic resonance spectroscopy
We examined the role of the large conductance voltage‐ and Ca 2+ ‐activated K + (BK) channels as non‐genomic targets for 17β‐estradiol in guinea pig urinary bladder smooth muscle (UBSM). We performed single BK channel recordings on inside‐out excised membrane patches and amphotericin‐B perforated whole cell patch‐clamp in combination with the BK channel inhibitor paxilline to determine the role of the BK channels as direct non‐genomic targets for 17β‐estradiol in UBSM cells. 17β‐estradiol (100 nM) significantly increased the amplitude of depolarization‐induced steady‐state whole cell K + currents and the frequency of transient BK currents in UBSM cells. The stimulatory effects on whole cell K + currents by 17β‐estradiol were blocked by the BK channel inhibitor paxilline (1 µM). 17β‐estradiol (100 nM) significantly increased the single BK channel open probability, indicating direct activation of the BK channels. 17β‐estradiol (100 nM) caused a significant hyperpolarization of the resting membrane potential of UBSM cells, and this hyperpolarization was reversed by blocking the BK channels with paxilline (1 µM). 17β‐estradiol (100 nM) had no inhibitory effects on L‐type voltage‐gated Ca 2+ channels. These data support a critical role for the BK channels as direct non‐genomic targets for 17β‐estradiol in UBSM cells, thus regulating UBSM excitability and contractility. Supported by NIH R01‐DK04284 to Georgi V. Petkov & NIH F31DK104528 to Aaron Provence.