Reduced Ca2+ spark activity contributes to detrusor overactivity of rats with partial bladder outlet obstruction
Reduced Ca2+ spark activity contributes to detrusor overactivity of rats with partial bladder outlet obstruction
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Ca2火花活性降低导致部分膀胱出口梗阻大鼠逼尿肌过度活动
DOI：
10.18632/aging.102855
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发表时间：
2020-02
期刊：
影响因子：
5.2
通讯作者：
Zhou Zhansong
中科院分区：
文献类型：
--
作者：
Zheng Ji;Zhou Hao;Yang Mengjun;Song Siji;Dai Qiang;Ji Guangju;Zhou Zhansong
我们检测了部分膀胱出口梗阻(PBOO)后Wistar大鼠逼尿肌过度活动(DO)是否与钙离子火花活性改变有关。我们通过PBOO建立了DO模型，研究了逼尿肌钙离子的放电活动。采用共聚焦显微镜和膜片钳技术，分别测定逼尿肌细胞的钙火花和自发瞬时外向电流(STOCs)。结果表明，DO逼尿肌细胞的钙离子放电活性和STOCs均显著低于正常对照细胞，而RyR激动剂咖啡因(10μM)对DO逼尿肌细胞的钙激活活性和STOC水平均有显著升高。此外，使用新鲜分离的逼尿肌条也记录了逼尿肌收缩的测量。结果表明，BK通道阻断剂Iberiooxin(100 NM)可显著增强DO逼尿肌的自发收缩，并逆转咖啡因(10μM)对DO逼尿肌收缩的影响。Western blotting(WB)分析显示，DO大鼠膀胱肌组织中RyR2和FK506结合蛋白12.6的表达水平分别降低和升高。因此，我们认为在大鼠DO模型中，PBOO，逼尿肌细胞内钙离子火花活性的降低部分是导致逼尿肌过度收缩的原因。RyR2表达降低和FKBP12.6表达增加可能是导致钙离子火花活性降低的原因之一。我们研究中的这些新发现可能有助于为患有膀胱功能障碍的患者提供更好的治疗结果。
We tested whether or not altered Ca2+ spark activity accounted for detrusor overactivity (DO) of Wistar rats after partial bladder outlet obstruction (PBOO). We constructed a DO model through PBOO and studied the Ca2+ spark activity of detrusor. By way of using confocal microscopy and the patch-clamp technique, Ca2+ sparks and spontaneous transient outward currents (STOCs) in detrusor myocytes were measured respectively. Our results indicated that Ca2+ spark activity and STOCs were significantly reduced in the DO detrusor myocytes compared to unafflicted control cells, and both of these had levels that were remarkably increased by applications of caffeine (10 μM), a RyR agonist, in DO myocytes. In addition, measures of detrusor contractions were also recorded by using freshly isolated detrusor strips. These results indicated that the spontaneous contraction of DO detrusor was significantly enhanced, and that the effect of caffeine (10 μM) upon detrusor contractions was reversed by applications of iberiotoxin (100 nM) which is a BK channel blocker. Western blotting (WB) analyses indicated that the levels of expression of ryanodine receptor type 2 (RyR2) and FK506 binding protein 12.6 (FKBP12.6) in bladder muscle were respectively decreased and increased in the samples from DO rats. Thus, we considered in the rat DO model wherein PBOO, the reduced Ca2+ spark activity in detrusor myocytes partly contributed to overactive detrusor contractions. The impaired Ca2+ spark activity may have resulted from decreased RyR2 expression and increased FKBP12.6 expression. Such novel findings in our research might help to provide means for better treatment outcomes for patients afflicted by bladder dysfunction.
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影响因子：
2.7
作者：
J. Long;Saif S. Khairat;Elizabeth A. Chmelo;M. Palmer
通讯作者：
J. Long;Saif S. Khairat;Elizabeth A. Chmelo;M. Palmer
影响因子：
1.6
作者：
P. Bulmer;P. Abrams
通讯作者：
P. Bulmer;P. Abrams
影响因子：
2.5
作者：
A. Tubaro;S. Mariani;C. de Nunzio;R. Miano
通讯作者：
A. Tubaro;S. Mariani;C. de Nunzio;R. Miano
DOI：
10.4140/tcp.n.2016.412
发表时间：
2016-01-01
期刊：
The Consultant pharmacist : the journal of the American Society of Consultant Pharmacists
影响因子：
--
作者：
Woodard, Todd J;Manigault, Kendra R;Woodard, Laresa M
通讯作者：
Woodard, Laresa M
影响因子：
3.7
作者：
Provence A;Hristov KL;Parajuli SP;Petkov GV
通讯作者：
Petkov GV