Regulation of urinary bladder smooth muscle contractions by ryanodine receptors and BK and SK channels

Regulation of urinary bladder smooth muscle contractions by ryanodine receptors and BK and SK channels
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DOI:
10.1152/ajpregu.2000.279.1.r60
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发表时间:
2000-07-01
影响因子:
2.8
通讯作者:
Nelson, MT
Nelson, MT
中科院分区:
医学3区
文献类型:
--
作者:
Herrera, GM;Heppner, TJ;Nelson, MT

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本研究探讨了电压依赖性 Ca2+ 通道 (VDCC)、兰尼碱受体 (RyRs)、大电导 Ca2+ 激活 K+ (BK) 通道和小电导 Ca2+ 激活 K+ (SK) 通道在调节豚鼠膀胱平滑肌 (UBSM) 阶段性收缩中的作用。 Nisoldipine (100 nM) 是一种 VDCC 的二氢吡啶抑制剂,可消除自发的 UBSM 收缩。 Ryanodine (10 μM) 增加了收缩频率,从而增加了综合力,并且在 SK 阻滞剂 apamin 存在的情况下,对综合力的影响比单独的 ryanodine 更大。阻断 BK(伊比利亚毒素,100 nM)或 SK(apamin,100 nM)通道会增加收缩幅度和持续时间,但会降低频率。对伊比利亚毒素的收缩反应比对 apamin 的收缩反应更明显。兰尼定预处理显着增强了 apamin 的收缩幅度和持续时间的增加。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具有显着的作用。 RyRs 似乎还作为收缩频率和持续时间的负反馈调节器发挥着重要作用,并且这种作用受到 SK 通道活动的影响。
This study examines the roles of voltage-dependent Ca2+ channels (VDCC), ryanodine receptors (RyRs), large-conductance Ca2+-activated K+ (BK) channels, and small-conductance Ca2+-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 mu M) 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.