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

1. ENaC在人膀胱中的表达：每个ENaC亚基（α、β和γ）在正常膀胱中的表达极低。然而，每个ENaC亚基在膀胱上皮中的表达水平在人梗阻膀胱中显著增加。上皮中ENaC的定量表达与储存症状评分显著相关. ENaC在大鼠膀胱中的表达：在大鼠正常膀胱上皮中，ENaC的α、β和γ亚基蛋白和基因均被清楚地表达。因此，ENaC在膀胱上皮中的表达在大鼠和人之间显示出显著的种属差异。在用抗CGRP抗体对大鼠膀胱粘膜进行免疫荧光双重染色时，只有一小部分CGRP免疫反应阳性的感觉神经末梢共表达ENaC。ENaC在排尿反射中的作用：在持续输注生理盐水的膀胱测压中，膀胱内灌注1 mM阿米洛利显著降低反射性排尿频率 ...更多信息 在膀胱充盈期间。阿米洛利的这种作用可以通过洗脱药物而逆转。阿米洛利对排尿压峰值无影响. ENaC在牵张诱发的膀胱上皮ATP释放中的作用：将具有或不具有上皮的膀胱条悬浮在器官浴中，进行不同程度的机械牵张。利用精氨酸荧光素酶分析，我们发现牵张引起的ATP释放，其中大部分是（90%以上）来自上皮层，被1 mM阿米洛利大大降低（从443增加到22%，从基础水平在50%的原始长度拉伸）。这些发现表明，阿米洛利-在大鼠膀胱上皮中表达的敏感钠通道通过控制牵张诱发的ATP释放参与机械感觉转导机制。膀胱上皮ENaC表达的增加可能改变了传入活动，这参与了膀胱出口梗阻引起的逼尿肌不稳定的诱导。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