Herrera G M, Heppner T J, Nelson M T
Department of Molecular Physiology and Biophysics, University of Vermont College of Medicine, Burlington, Vermont 05405, USA.
Am J Physiol Regul Integr Comp Physiol. 2000 Jul;279(1):R60-8. doi: 10.1152/ajpregu.2000.279.1.R60.
This study examines the roles of voltage-dependent Ca(2+) channels (VDCC), ryanodine receptors (RyRs), large-conductance Ca(2+)-activated K(+) (BK) channels, and small-conductance Ca(2+)-activated K(+) (SK) channels in the regulation of phasic contractions of guinea pig urinary bladder smooth muscle (UBSM). Nisoldipine (100 nM), a dihydropyridine inhibitor of VDCC, abolished spontaneous UBSM contractions. Ryanodine (10 microM) increased contraction frequency and thereby integrated force and, in the presence of the SK blocker apamin, had a greater effect on integrated force than ryanodine alone. Blocking BK (iberiotoxin, 100 nM) or SK (apamin, 100 nM) channels increased contraction amplitude and duration but decreased frequency. The contractile response to iberiotoxin was more pronounced than to apamin. The increases in contraction amplitude and duration to apamin were substantially augmented with ryanodine pretreatment. These results indicate that BK and SK channels have prominent roles as negative feedback elements to limit UBSM contraction amplitude and duration. RyRs also appear to play a significant role as a negative feedback regulator of contraction frequency and duration, and this role is influenced by the activity of SK channels.
本研究考察电压依赖性钙通道（VDCC）、兰尼碱受体（RyR）、大电导钙激活钾通道（BK）和小电导钙激活钾通道（SK）在豚鼠膀胱平滑肌（UBSM）相性收缩调节中的作用。硝苯地平（100 nM），一种VDCC的二氢吡啶抑制剂，消除了UBSM的自发性收缩。兰尼碱（10 μM）增加了收缩频率，从而整合了力量，并且在存在SK阻滞剂蜂毒明肽的情况下，对整合力量的影响比单独使用兰尼碱时更大。阻断BK通道（iberiotoxin，100 nM）或SK通道（蜂毒明肽，100 nM）增加了收缩幅度和持续时间，但降低了频率。对iberiotoxin的收缩反应比对蜂毒明肽更明显。用兰尼碱预处理后，对蜂毒明肽的收缩幅度和持续时间的增加显著增强。这些结果表明，BK和SK通道作为负反馈元件在限制UBSM收缩幅度和持续时间方面发挥着重要作用。RyR似乎也作为收缩频率和持续时间的负反馈调节因子发挥着重要作用，并且这一作用受SK通道活性的影响。
