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Inhibition of phosphodiesterases relaxes urinary bladder smooth muscle via activation of the large conductance voltageand Ca 2+ ‐activated K + channels
Author(s) -
Xin Wenkuan,
Cheng Qiuping,
Soder Rupal P.,
Petkov Georgi V.
Publication year - 2012
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.26.1_supplement.1140.10
Subject(s) - ibmx , contractility , chemistry , membrane potential , hyperpolarization (physics) , biophysics , bk channel , depolarization , phosphodiesterase , carbachol , endocrinology , medicine , stimulation , biology , biochemistry , stereochemistry , forskolin , nuclear magnetic resonance spectroscopy , enzyme
Our previous studies showed that activation of cAMP signaling pathways reduces urinary bladder smooth muscle (UBSM) contractility by increasing the large conductance Ca 2+ ‐activated K + (BK) channel activity. Utilizing isometric UBSM tension recordings and the perforated patch‐clamp technique, we tested the hypothesis whether inhibition of phosphodiesterases (PDEs) can reduce guinea pig UBSM excitability and contractility by increasing BK channel activity. Inhibition of PDEs by 3‐isobutyl‐1‐methylxanthine (IBMX) concentration‐dependently reduced UBSM spontaneous and carbachol‐induced phasic contractions. IBMX also reduced electrical field stimulation (0.5–50 Hz)‐induced contractions of UBSM strips. Blocking BK channels with paxilline diminished the inhibitory effects of IBMX on UBSM contractility. IBMX increased the transient BK currents (TBKCs) frequency by ~3‐fold. However, IBMX did not affect the depolarization‐induced steady‐state whole‐cell BK currents. IBMX increased the frequency of the spontaneous transient hyperpolarizations by ~2‐fold and hyperpolarized the UBSM cell resting membrane potential by ~6 mV. Blocking the BK channels abolished the IBMX effect on the resting membrane potential. Our data reveal that PDEs inhibition with IBMX relaxes guinea pig UBSM via TBKCs activation and subsequent UBSM cell membrane hyperpolarization. Supported by NIH DK084284 to G.V.P.