BK channel activation by NS11021 decreases excitability and contractility of urinary bladder smooth muscle

Jeffrey J. Layne, Bernhard Nausch, Søren Peter Olesen, Mark T. Nelson

    Research output: Contribution to journalArticlepeer-review

    Abstract

    Large-conductance Ca2+-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 μM) caused an approximately threefold increase in both single BK channel open probability (Po) 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 ± 5.9 to 10.9 ± 3.7 per minute. NS11021 also reduced the force of UBSM spontaneous phasic contractions by ̃50%, and this force reduction was blocked by pretreatment with the BK channel blocker iberiotoxin. NS11021 (3 μM) 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. Copyright © 2010 the American Physiological Society.
    Original languageEnglish
    Pages (from-to)R378-R384
    JournalAJP: Regulatory, Integrative and Comparative Physiology
    Volume298
    Issue number2
    DOIs
    Publication statusPublished - Feb 2010

    Keywords

    • Calcium-activated potassium channel opener
    • Detrusor contractility
    • Urinary bladder smooth muscle

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