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BK Channel Activation by NS11021 Decreases Excitability and Contractility of Urinary Bladder Smooth Muscle.
American journal of physiology. Regulatory, integrative and comparative physiology 2009 Nov 18; In press
Layne J JJ, Nausch B, Olesen S SP, Nelson M MT
University of Vermont.
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 a ~3-fold 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 / min to 10.9 +/- 3.7 / min. NS11021 also reduced the force of UBSM spontaneous phasic contractions (SPCs) by ~50%, and this force reduction was blocked by pre-treatment with the BK channel blocker iberiotoxin. NS11021 (3muM) 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. Key words: detrusor contractility, urinary bladder smooth muscle, BK, NS11021.