Effects of different types of K+ channel modulators on the spontaneous myogenic contraction of guinea-pig urinary bladder smooth muscle
Effects of different types of K+ channel modulators on the spontaneous myogenic contraction of guinea-pig urinary bladder smooth muscle
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DOI：
10.1046/j.1365-201x.2001.00908.x
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发表时间：
2001-11-01
期刊：
影响因子：
--
通讯作者：
Tanaka, Y
中科院分区：
文献类型：
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作者：
Imai, T;Okamoto, T;Tanaka, Y
在本研究中，研究了不同类型的 K+ 通道调节剂对豚鼠膀胱平滑肌 (UBSM) 自发节律收缩活动的影响。豚鼠UBSM在阿托品（1μM）、酚妥拉明（1μM）、普萘洛尔（1μM）、苏拉明（10μM）和河豚毒素（1μM）存在下表现出肌源性节律性收缩。尼索地平 (100 nM) 或地尔硫卓 (10 muM) 显着降低 UBSM 收缩活性。 UBSM 节律性收缩的尼索地平耐药成分被钆 (200 muM) 进一步抑制。 Iberiotoxin (50 nM) 是一种大电导、电压门控 Ca2+ 激活的 K+ (K-Ca) (BK) 通道的选择性阻断剂，可显着增加收缩幅度和频率，而增加 BK 通道活性的 NS-1619 (30 muM) 则可降低收缩幅度和频率。 Apamin (100 nM) 是一种小电导 K-Ca (SK) 通道的选择性阻断剂，可增加收缩幅度但降低频率。电压门控 K+ (K-v) 通道阻断剂 4-氨基吡啶 (100 muM) 显着增加收缩频率，E-4031 是一种新型内向整流 K+ 通道（即人 ether-a-go-go 相关基因 (HERG) K+ 通道）阻断剂，显着增加收缩幅度，格列本脲 (1-10 muM)（K-ATP 通道阻断剂）和 Ba2+ (10 muM）（传统的 K-ir 通道阻断剂）对 UBSM 的自发收缩活性没有表现出明显的影响。这些发现意味着两种类型的 Kc。 (BK 和 SK) 通道作为负反馈元件发挥着重要作用，通过调节幅度和频率来限制细胞外 Ca2+ 内流介导的豚鼠 UBSM 收缩。还提出非 K-Ca 型 K+（K-v 和 HERG 样 K+）通道可能有助于调节 UBSM 肌源性节律性收缩。
In the present study, effects of different types of K+ channel modulators on the spontaneous rhythmic contractile activity were examined in guinea-pig urinary bladder smooth muscle (UBSM). Guinea-pig UBSM exhibited myogenic rhythmic contraction in the presence of atropine (1 muM), phentolamine (1 muM), propranolol (1 muM), suramin (10 muM) and tetrodotoxin (1 muM). Nisoldipine (100 nM) or diltiazem (10 muM) substantially diminished UBSM contractile activity. Nisoldipine-resistant component of UBSM rhythmic contraction was further inhibited by gadolinium (200 muM). Iberiotoxin (50 nM), a selective blocker of large-conductance, voltage-gated Ca2+-activated K+ (K-Ca) (BK) channel, dramatically increased both contraction amplitude and frequency whereas NS-1619 (30 muM), which increases BK channel activity, decreased them. Apamin (100 nM), a selective blocker of small-conductance, K-Ca (SK) channel, increased contraction amplitude but decreased frequency. A blocker of voltage-gated K+ (K-v) channel, 4-aminopyridine (100 muM), significantly increased contraction frequency, E-4031, a blocker of a novel inwardly rectifying K+ channel, i.e. the human ether-a-go-go-related gene (HERG) K+ channel, significantly increased contraction amplitude, Glibenclamide (1-10 muM) (K-ATP channel blocker) and Ba2+ (10 muM) (conventional K-ir channel blocker) did not exhibit conspicuous effects on spontaneous contractile activity of UBSM. These findings imply that two types of Kc. (BK and SK) channels have prominent roles as negative feedback elements to limit extracellular Ca2+ influx-mediated guinea-pig UBSM contraction by regulating both amplitude and frequency. It was also suggested that both non-K-Ca type of K+ (K-v and HERG-like K+) channels may contribute to the regulation of UBSM myogenic rhythmic contraction.