Role of ENaC/Deg.Channel Family in Afferent Transduction of Lower Urinary Tract.

1. ENaC在人膀胱中的表达：ENaC各亚基（α、β和γ）在正常膀胱中的表达极低。然而，在人膀胱梗阻中，各ENaC亚基在膀胱上皮中的表达水平显著升高。上皮内ENaC定量表达与贮藏症状评分显著相关。ENaC在大鼠膀胱中的表达：ENaC亚基（α、β和γ）蛋白和基因在大鼠正常膀胱上皮中均可见。因此，ENaC在膀胱上皮中的表达在大鼠和人之间表现出显著的物种差异。2 .用抗cgrp抗体对大鼠膀胱黏膜进行双免疫荧光染色时，只有一小部分cgrp免疫反应性感觉神经末梢共表达enact。ENaC在排尿反射中的作用：在连续生理盐水输注膀胱术中，膀胱内灌注1mM阿米洛利可显著降低排尿反射频率。阿米洛利的这种作用通过冲洗药物是可逆的。排尿压力峰幅不受阿米洛利德的影响。ENaC在拉伸诱导的膀胱上皮ATP释放中的作用：有或没有上皮的膀胱条悬浮在器官浴中，受到不同程度的机械拉伸。通过荧光素-荧光素酶测定，我们发现拉伸引起的ATP释放，其中大部分（超过90%）来自上皮层，在1mM阿米洛利的作用下大大减少（在原始长度的50%拉伸时，从基础水平增加443到22%）。这些结果表明，大鼠膀胱上皮中表达的阿米洛利钠敏感通道通过控制拉伸引起的ATP释放参与机械感觉转导机制。ENaC在人膀胱上皮中的表达增加可能会改变传入神经的活性，这可能与膀胱出口梗阻引起的逼尿肌不稳定有关。少

1. ENaC expression in the human urinary bladder :The expression of each ENaC subunit (α, β and γ) was extremely poor in normal bladders. However, the expression levels of each ENaC subunit in the bladder epithelium were significantly increased in human obstructed bladders. The quantified ENaC expression in the epithelium was significantly correlated with storage symptom score.2. ENaC expression in the rat urinary bladder :All ENaC subunit (α, β and γ) proteins and genes were clearly detected in the rat normal bladder epithelium. Thus, ENaC expression in the bladder epithelium showed a remarkable species difference between the rat and human. In double immunofluoresent staining of rat bladder mucosa with anti-CGRP antibodies, only a small part of CGRP-immunoreactive sensory nerve terminals co-expressed ENaC.3. Role of ENaC in micturition reflex :In cystometry with continuous saline infusion, the intravesical perfusion of 1mM amiloride significantly reduced the frequency of reflex voiding … More during bladder filling. This effect of amiloride was reversible by washing out the drug. The peak amplitude of micturition pressure was not affected by amiloride.4. Role of ENaC in stretch-evoked ATP release from bladder epithelium :Bladder strips with or without epithelium suspended in organ bath were subjected to varying degrees of mechanical stretch. Using luciferine-luciferase assay, we found that the stretch-evoked ATP release, a majority of which (over 90%) came from epithelial layer, was greatly diminished by 1mM amiloride (from 443 to 22% increase from basal level at 50% stretch of original length).These findings indicate that the amiloride-sensitive sodium channels expressed in the rat bladder epithelium participate in the mechanosensory transduction mechanism by controlling stretch-evoked ATP release. The increased ENaC expression in the human bladder epithelium might change the afferent activity, which is involved in the induction of detrusor instability due to bladder outlet obstruction. Less