Identification of large conductance calcium activated potassium channel accessory beta4 subunit in rat and mouse bladder smooth muscle.
Identification of large conductance calcium activated potassium channel accessory beta4 subunit in rat and mouse bladder smooth muscle.
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DOI：
10.1016/j.juro.2009.02.109
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发表时间：
2009-07
期刊：
影响因子：
--
通讯作者：
Petkov GV
中科院分区：
文献类型：
--
作者：
Chen M;Petkov GV
BK（大电导电压和Ca 2+激活的K+）通道是膀胱平滑肌收缩的关键调节器。据我们所知，在膀胱平滑肌中，BK通道孔形成α亚基BKα与4种调节性平滑肌特异性β1亚基以同源四聚体形式缔合。我们对这一概念提出了挑战，以确定小鼠和大鼠膀胱平滑肌中是否存在其他调节性BKβ亚基。我们使用了一种新的方法，单细胞逆转录聚合酶链反应结合免疫细胞化学研究在新鲜分离的小鼠和大鼠膀胱平滑肌细胞。还进行了Western印迹。逆转录-聚合酶链反应鉴定了新鲜分离的膀胱平滑肌细胞中各种BK通道亚基的mRNA表达。我们的数据表明，除了BKα和BKβ1，神经元特异性BKβ4在小鼠和大鼠膀胱平滑肌细胞中表达。Western blot检测BKβ4表达。免疫细胞化学染色证实BKβ4蛋白在新鲜分离的小鼠和大鼠膀胱平滑肌细胞中特异性表达。据我们所知，我们进行了第一次全面的检查，BKα和BKβ亚基在膀胱平滑肌的表达。我们发现，膀胱平滑肌BK通道具有独特的结构，涉及孔形成BKα和调节BKβ1/β4。进一步研究BKα、BKβ1和BKβ4在人膀胱平滑肌中的功能作用可能有助于开发控制膀胱功能障碍的替代治疗策略。靶向人膀胱平滑肌特异性BK通道亚单位的新药可能对膀胱过度活动症有用。
The BK (large conductance voltage and Ca2+ activated K+) channel is a key regulator of bladder smooth muscle contractility. To our knowledge in bladder smooth muscle the BK channel pore forming α subunit BKα associates in homotetramers with 4 regulatory smooth muscle specific β1 subunits. We challenged this concept in identify whether other regulatory BKβ subunits exist in mouse and rat bladder smooth muscle. We used a novel approach with single cell reverse transcriptase-polymerase chain reaction combined with immunocytochemical studies in freshly isolated mouse and rat bladder smooth muscle cells. Western blot was also performed. Reverse transcriptase-polymerase chain reaction identified the mRNA expression of various BK channel subunits in freshly isolated bladder smooth muscle cells. Our data indicate that, in addition to BKα and BKβ1, neuronal specific BKβ4 is expressed in mouse and rat bladder smooth muscle cells. BKβ4 expression was also revealed by Western blot. Immunocytochemistry was further applied to confirm the specific expression of BKβ4 protein directly in freshly isolated mouse and rat bladder smooth muscle cells. To our knowledge we performed the first comprehensive examination of the expression of BKα and BKβ subunits in bladder smooth muscle. We identified that the bladder smooth muscle BK channel has a distinctive architecture involving pore forming BKα and regulatory BKβ1/β4. Further studies of the functional roles of BKα, BKβ1 and BKβ4 directly in human bladder smooth muscle may help the development of alternative therapeutic strategies to control bladder dysfunction. New drugs targeting specific BK channel subunits in human bladder smooth muscle may prove useful for overactive bladder.
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DOI：
10.1152/nips.01387.2002
发表时间：
2002-08-01
期刊：
NEWS IN PHYSIOLOGICAL SCIENCES
影响因子：
--
作者：
Orio, P;Rojas, P;Latorre, R
通讯作者：
Latorre, R
DOI：
10.1152/ajprenal.00018.2007
发表时间：
2007-07-01
影响因子：
4.2
作者：
Grimm, P. Richard;Foutz, Ruth M.;Sansom, Steven C.
通讯作者：
Sansom, Steven C.
影响因子：
4.8
作者：
Brenner, R;Jegla, TJ;Aldrich, RW
通讯作者：
Aldrich, RW
DOI：
10.1085/jgp.116.3.411
发表时间：
2000-09
期刊：
The Journal of general physiology
影响因子：
--
作者：
Cox DH;Aldrich RW
通讯作者：
Aldrich RW
影响因子：
3.5
作者：
Behrens, R;Nolting, A;Pongs, O
通讯作者：
Pongs, O