Abstract
Our previous studies showed that activation of cAMP signaling pathways reduces urinary bladder smooth muscle (UBSM) contractility by increasing the large conductance Ca2+‐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.
Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
