Voltage-gated K+ channels sensitive to stromatoxin-1 regulate myogenic and neurogenic contractions of rat urinary bladder smooth muscle
Voltage-gated K+ channels sensitive to stromatoxin-1 regulate myogenic and neurogenic contractions of rat urinary bladder smooth muscle
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DOI：
10.1152/ajpregu.00036.2010
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发表时间：
2010-07-01
影响因子：
2.8
通讯作者：
Petkov, Georgi V.
中科院分区：
文献类型：
--
作者：
Chen, Muyan;Kellett, Whitney F.;Petkov, Georgi V.
Chen M，Kellett WF，Petkov GV.对stromatoxin-1敏感的电压门控性K+通道调节大鼠膀胱平滑肌的肌源性和神经源性收缩Am J Physiol Regul Integr Comp Physiol 299：R177-R184，2010.首次发表于2010年4月14日; doi：10.1152/ajpregu.00036.2010。电压门控性钾离子通道家族的成员被认为控制着膀胱平滑肌的静息膜电位和动作电位的复极相。最近的研究报道，从狼蛛中分离的肽Stromatoxin-1选择性地抑制K（V）2.1、K（V）2.2、K（V）4.2和K（V）2.1/9.3通道。本研究的目的是探讨是否敏感的K-V通道stromatoxin-1参与调节大鼠UBSM收缩，并确定其分子指纹。Stromatoxin-1（100 nM）增加了孤立的UBSM条的自发阶段性收缩幅度，肌肉力量和张力。然而，stromatoxin-1（100 nM）对去极化剂如KCl（20 mM）或卡巴胆碱（1 μ M）诱导的UBSM收缩没有影响。这表明，在持续的膜去极化的条件下，对stromatoxin-1敏感的K-V通道对膜的兴奋性和收缩性没有进一步的贡献。Stromatoxin-1（100 nM）增加了电场刺激诱导的收缩幅度，这也表明这些通道在神经性收缩中的作用。对新鲜分离的UBSM细胞的RT-PCR实验显示K（V）2.1、K（V）2.2和K（V）9.3通道亚基的mRNA表达，但不显示K（V）4.2通道亚基。用Western blot检测K（V）2.1和K（V）2.2通道的蛋白表达，并通过免疫细胞化学检测在新鲜分离的UBSM细胞中进一步证实。这些新的发现表明，K（V）2.1和K（V）2.2，而不是K（V）4.2，通道亚基在大鼠UBSM中表达，并在对抗肌源性和神经源性UBSM收缩中发挥关键作用。
Chen M, Kellett WF, Petkov GV. Voltage-gated K+ channels sensitive to stromatoxin-1 regulate myogenic and neurogenic contractions of rat urinary bladder smooth muscle. Am J Physiol Regul Integr Comp Physiol 299: R177-R184, 2010. First published April 14, 2010; doi:10.1152/ajpregu.00036.2010.-Members of the voltage-gated K+ (K-V) channel family are suggested to control the resting membrane potential and the repolarization phase of the action potential in urinary bladder smooth muscle (UBSM). Recent studies report that stromatoxin-1, a peptide isolated from tarantulas, selectively inhibits K(V)2.1, K(V)2.2, K(V)4.2, and K(V)2.1/9.3 channels. The objective of this study was to investigate whether K-V channels sensitive to stromatoxin-1 participate in the regulation of rat UBSM contractility and to identify their molecular fingerprints. Stromatoxin-1 (100 nM) increased the spontaneous phasic contraction amplitude, muscle force, and tone in isolated UBSM strips. However, stromatoxin-1 (100 nM) had no effect on the UBSM contractions induced by depolarizing agents such as KCl (20 mM) or carbachol (1 mu M). This indicates that, under conditions of sustained membrane depolarization, the K-V channels sensitive to stromatoxin-1 have no further contribution to the membrane excitability and contractility. Stromatoxin-1 (100 nM) increased the amplitude of the electrical field stimulation-induced contractions, suggesting also a role for these channels in neurogenic contractions. RT-PCR experiments on freshly isolated UBSM cells showed mRNA expression of K(V)2.1, K(V)2.2, and K(V)9.3, but not K(V)4.2 channel subunits. Protein expression of K(V)2.1 and K(V)2.2 channels was detected using Western blot and was further confirmed by immunocytochemical detection in freshly isolated UBSM cells. These novel findings indicate that K(V)2.1 and K(V)2.2, but not K(V)4.2, channel subunits are expressed in rat UBSM and play a key role in opposing both myogenic and neurogenic UBSM contractions.