Large conductance Ca2+ -activated K+ channel activation with NS1619 decreases myogenic and neurogenic contractions of rat detrusor smooth muscle.
Large conductance Ca2+ -activated K+ channel activation with NS1619 decreases myogenic and neurogenic contractions of rat detrusor smooth muscle.
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DOI：
10.1016/j.ejphar.2011.08.013
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发表时间：
2011-11-16
影响因子：
5
通讯作者：
Petkov, Georgi V.
中科院分区：
文献类型：
--
作者：
Soder, Rupal P.;Petkov, Georgi V.
大电导电压和Ca 2+激活的K+通道在调节逼尿肌平滑肌（DSM）功能中是重要的。在这里，我们系统地研究了BK通道药理学激活如何调节DSM收缩性。NS 1619是一种有效的BK通道激活剂，被用作药理学工具来研究BK通道激活对大鼠DSM收缩性的影响。在各种实验条件下，系统地进行了大鼠膀胱DSM条的等长张力记录。NS 1619（30 μM）显著降低DSM自发收缩幅度、肌力积分、频率、持续时间和肌张力。此作用可被BK通道选择性抑制剂伊比利亚毒素阻断。NS 1619可抑制用胆碱能激动剂卡巴胆碱（0.1 μM）或去极化剂KCl（20 mM和60 mM KCl）预收缩的DSM条中的相位性和强直性收缩。在KCl升高的情况下，NS 1619的抑制作用显著降低，表明BK通道激活是NS 1619作用的潜在机制。在一定范围的刺激频率（0.5-50 Hz）下，用NS 1619激活BK通道显著降低了电场刺激（EFS）诱导的收缩的幅度。在特定的神经递质抑制剂的存在下，BK通道激活与NS 1619显着降低胆碱能和嘌呤能成分的EFS诱导的收缩。我们的结论是，BK通道激活与NS 1619显着抑制自发，电刺激诱导和神经诱发的DSM收缩。用选择性开放剂靶向BK通道可以提供控制DSM收缩活动的独特机会，包括病理生理学状况，如膀胱过度活动症和逼尿肌过度活动症，而不管潜在原因。
Large conductance voltage- and Ca2+-activated K+ channels are important in regulating detrusor smooth muscle (DSM) function. Here, we examined systematically how the BK channel pharmacological activation modulates DSM contractility. NS1619, a potent BK channel activator, was utilized as a pharmacological tool to investigate the effect of BK channel activation on rat DSM contractility. Isometric tension recordings of DSM strips isolated from rat urinary bladder were performed systematically under various experimental conditions. NS1619 (30 μM) substantially diminished DSM spontaneous contraction amplitude, muscle force integral, frequency, duration and muscle tone. This effect was blocked by iberiotoxin, a BK channel selective inhibitor. NS1619 inhibited the phasic and tonic contractions in DSM strips pre-contracted with either the cholinergic agonist, carbachol (0.1 μM), or the depolarizing agent, KCl (20 mM and 60 mM KCl). In the presence of elevated KCl, the inhibitory effect of NS1619 was significantly reduced, indicating that BK channel activation is the underlying mechanism of NS1619 action. BK channel activation with NS1619 dramatically decreased the amplitude of electrical field stimulation (EFS)-induced contractions under a range of stimulation frequencies (0.5–50 Hz). In the presence of specific neurotransmitter inhibitors, BK channel activation with NS1619 significantly decreased both cholinergic and purinergic components of EFS-induced contractions. We conclude that BK channel activation with NS1619 significantly inhibited spontaneous, pharmacologically induced and nerve-evoked DSM contractions. Targeting the BK channel with selective openers may offer a unique opportunity to control DSM contractile activity, including pathophysiological conditions such as overactive bladder and detrusor overactivity, regardless of the underlying cause.
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影响因子：
4.8
作者：
Brenner, R;Jegla, TJ;Aldrich, RW
通讯作者：
Aldrich, RW
DOI：
10.1046/j.1365-201x.2001.00908.x
发表时间：
2001-11-01
期刊：
ACTA PHYSIOLOGICA SCANDINAVICA
影响因子：
--
作者：
Imai, T;Okamoto, T;Tanaka, Y
通讯作者：
Tanaka, Y
DOI：
10.1152/ajpregu.00036.2010
发表时间：
2010-07-01
影响因子：
2.8
作者：
Chen, Muyan;Kellett, Whitney F.;Petkov, Georgi V.
通讯作者：
Petkov, Georgi V.
影响因子：
7.3
作者：
EDWARDS, G;NIEDERSTEHOLLENBERG, A;WESTON, AH
通讯作者：
WESTON, AH
DOI：
10.1152/ajpregu.2001.280.5.r1427
发表时间：
2001-05-01
影响因子：
2.8
作者：
Petkov, GV;Heppner, TJ;Nelson, MT
通讯作者：
Nelson, MT