Comparison of mechanical and electrical activity and interstitial cells of Cajal in urinary bladders from wild-type and W/Wv mice

Comparison of mechanical and electrical activity and interstitial cells of Cajal in urinary bladders from wild-type and W/Wv mice
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DOI:
10.1111/j.1476-5381.2008.00006.x
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发表时间:
2009-01-01
影响因子:
7.3
通讯作者:
Ward, S. M.
Ward, S. M.
中科院分区:
医学2区
文献类型:
--
作者:
McCloskey, K. D.;Anderson, U. A.;Ward, S. M.

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研究W/W-v和野生型鼠膀胱以确定W/W-v表型是否是研究膀胱Cajal间质细胞(ICC)功能的有用工具,W/W-v表型引起酪氨酸激酶活性的降低但不消除。在野生型和突变型膀胱上进行张力记录和膜电位的微电极记录。野生型和W/W-v逼尿肌含有c-Kit,波形蛋白免疫阳性细胞的数量、分布和形态相当。电场刺激诱发野生型和W/W-v逼尿肌条的河豚毒素敏感性收缩。阿托品减少野生型反应的50%,而25%的减少发生在W/W-v条。在两种组织类型中,阿托品不敏感组分均被吡哆醛-5-磷酸-6-偶氮苯基-2 ',4'-二磺酸阻断。野生型和W/W-v逼尿肌的静息膜电位相似,均为-48 mV。两种组织类型的自发电活动包括动作电位和单位电位。动作电位是硝苯地平敏感,而单位电位不是。在两种组织中通过单脉冲诱发兴奋性连接电位。这些减少阿托品在野生型组织中,但不是在W/W-v制剂。在两种制剂中,5-磷酸吡哆醛-6-偶氮苯基-2 ',4'-二磺酸消除了阿托品不敏感成分。W/W-v小鼠膀胱含有c-Kit和波形蛋白免疫阳性ICC。W/W-v和野生型逼尿肌的电特性和收缩特性有相似之处。然而,显着的差异被发现在药理学的反应,以神经源性刺激与一个明显的上调嘌呤能成分。这些发现表明W/W-v株可能不是研究膀胱ICC功能的最佳模型。
W/W-v and wild-type murine bladders were studied to determine whether the W/W-v phenotype, which causes a reduction in, but not abolition of, tyrosine kinase activity, is a useful tool to study the function of bladder interstitial cells of Cajal (ICC).Immunohistochemistry, tension recordings and microelectrode recordings of membrane potential were performed on wild-type and mutant bladders.Wild-type and W/W-v detrusors contained c-Kit- and vimentin-immunopositive cells in comparable quantities, distribution and morphology. Electrical field stimulation evoked tetrodotoxin-sensitive contractions in wild-type and W/W-v detrusor strips. Atropine reduced wild-type responses by 50% whereas a 25% reduction occurred in W/W-v strips. The atropine-insensitive component was blocked by pyridoxal-5-phosphate-6-azophenyl-2',4'-disulphonic acid in both tissue types. Wild-type and W/W-v detrusors had similar resting membrane potentials of -48 mV. Spontaneous electrical activity in both tissue types comprised action potentials and unitary potentials. Action potentials were nifedipine-sensitive whereas unitary potentials were not. Excitatory junction potentials were evoked by single pulses in both tissues. These were reduced by atropine in wild-type tissues but not in W/W-v preparations. The atropine-insensitive component was abolished by pyridoxal-5-phosphate-6-azophenyl-2',4'-disulphonic acid in both preparations.Bladders from W/W-v mice contain c-Kit- and vimentin-immunopositive ICC. There are similarities in the electrical and contractile properties of W/W-v and wild-type detrusors. However, significant differences were found in the pharmacology of the responses to neurogenic stimulation with an apparent up-regulation of the purinergic component. These findings indicate that the W/W-v strain may not be the best model to study ICC function in the bladder.