title: BK channel activation by NS11021 decreases excitability and contractility of urinary bladder smooth muscle.
abstract: Large-conductance Ca(2+)-activated potassium (BK) channels play an important role in regulating the function and activity of urinary bladder smooth muscle (UBSM), and the loss of BK channel function has been shown to increase UBSM excitability and contractility. However, it is not known whether activation of BK channels has the converse effect of reducing UBSM excitability and contractility. Here, we have sought to investigate this possibility by using the novel BK channel opener NS11021. NS11021 (3 microM) caused an approximately threefold increase in both single BK channel open probability (P(o)) and whole cell BK channel currents. The frequency of spontaneous action potentials in UBSM strips was reduced by NS11021 from a control value of 20.9 + or - 5.9 to 10.9 + or - 3.7 per minute. NS11021 also reduced the force of UBSM spontaneous phasic contractions by approximately 50%, and this force reduction was blocked by pretreatment with the BK channel blocker iberiotoxin. NS11021 (3 microM) had no effect on contractions evoked by nerve stimulation. These findings indicate that activating BK channels reduces the force of UBSM spontaneous phasic contractions, principally through decreasing the frequency of spontaneous action potentials.
authors.affiliation: Department of Pharmacology, College of Medicine, University of Vermont, Burlington, VT 05405, USA.
authors.forename: Jeffrey J
authors.initials: JJ
authors.lastname: Layne
authors.forename: Bernhard
authors.initials: B
authors.lastname: Nausch
authors.forename: Søren-Peter
authors.initials: SP
authors.lastname: Olesen
authors.forename: Mark T
authors.initials: MT
authors.lastname: Nelson
mesh_terms: D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D004558:Electric Stimulation; D004594:Electrophysiology; D006168:Guinea Pigs; D066298:In Vitro Techniques; D051036:Large-Conductance Calcium-Activated Potassium Channels / Q000819:agonists*; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000166:cytology / Q000187:drug effects*; D018408:Patch-Clamp Techniques; D010455:Peptides / Q000494:pharmacology; D026902:Potassium Channel Blockers / Q000494:pharmacology; D013777:Tetrazoles / Q000494:pharmacology*; D013890:Thiourea / Q000031:analogs & derivatives* / Q000494:pharmacology; D001743:Urinary Bladder / Q000166:cytology / Q000187:drug effects*
chemical_list: C524410:1-(3,5-bis(trifluoromethyl)phenyl)-3-(4-bromo-2-(1H-tetrazol-5-yl)phenyl)thiourea; D051036:Large-Conductance Calcium-Activated Potassium Channels; D010455:Peptides; D026902:Potassium Channel Blockers; D013777:Tetrazoles; C064719:iberiotoxin; D013890:Thiourea