Department of Pharmacology, College of Medicine, University of Vermont, Burlington, VT 05405, USA.
Am J Physiol Regul Integr Comp Physiol. 2010 Feb;298(2):R378-84. doi: 10.1152/ajpregu.00458.2009. Epub 2009 Nov 18.
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.
大电导钙激活钾 (BK) 通道在调节膀胱平滑肌 (UBSM) 的功能和活性方面发挥着重要作用，而 BK 通道功能的丧失已被证明会增加 UBSM 的兴奋性和收缩性。然而，目前尚不清楚激活 BK 通道是否具有相反的作用，即降低 UBSM 的兴奋性和收缩性。在这里，我们试图通过使用新型 BK 通道 opener NS11021 来研究这种可能性。NS11021（3μM）使单个 BK 通道开放概率（P(o)）和全细胞 BK 通道电流增加约三倍。NS11021 将 UBSM 条带中的自发性动作电位频率从对照值 20.9 + or - 5.9 降低至 10.9 + or - 3.7 次/分钟。NS11021 还使 UBSM 自发性相收缩的力降低了约 50%，而这种力的降低被 BK 通道阻滞剂 Iberiotoxin 的预处理所阻断。NS11021（3μM）对神经刺激引起的收缩没有影响。这些发现表明，激活 BK 通道可降低 UBSM 自发性相收缩的力，主要是通过降低自发性动作电位的频率。
