Urogenix, Inc, PO Box 12035, Durham, NC 27709, USA.
J Physiol. 2010 Dec 15;588(Pt 24):4951-67. doi: 10.1113/jphysiol.2010.197319. Epub 2010 Oct 25.
The urethral rhabdosphincter (URS), commonly known as the external urethral sphincter, facilitates urinary continence by constricting the urethra. Striated muscle fibres in the urethral rhabdosphincter are innervated by Onuf's nuclei motoneurons in the spinal cord. Although noradrenaline (NA) reuptake inhibitors are shown to increase URS tone preventing urinary leakage in incontinent patients, whether or how NA affects URS motoneurons is unknown. Properties of dye-labelled URS motoneurons were investigated by whole-cell patch-clamp recordings in isolated spinal cord slices prepared from neonatal female rats. As previously shown for adult sphincter motoneurons, neonatal URS motoneurons are more depolarized and possess higher input resistance than other spinal α-motoneurons. These distinct properties make URS motoneurons more excitable than other α-motoneurons. Moreover, bath application of noradrenaline (NA) significantly depolarizes URS motoneurons and in many cases evokes action potentials. NA also significantly increases input resistance and reduces rheobase. These changes are reversed with wash, are largely blocked by the α(1)-adrenoceptor-selective antagonist prazosin, and are mimicked by the α(1)-adrenoceptor-selective agonist phenylephrine. In addition, NA significantly reduces the amplitude of the afterhyperpolarization and increases action potential frequency. Both the increase in action potential frequency and the reduction in afterhyperpolarization are occluded by apamin, a small-conductance calcium-activated potassium (SK(Ca)) channel blocker. In conclusion, NA effectively increases the excitability of URS motoneurons through multiple mechanisms. The NA-induced increase in excitability of urethral rhabdosphincter motoneurons could be a key mechanism by which NA reuptake inhibitors improve stress urinary incontinence.
尿道横纹括约肌（URS），通常称为尿道外括约肌，通过收缩尿道促进尿失禁。尿道横纹括约肌中的横纹肌纤维由脊髓中的 Onuf 核运动神经元支配。虽然去甲肾上腺素（NA）再摄取抑制剂被证明可以增加 URS 张力，防止失禁患者发生尿漏，但 NA 是否以及如何影响 URS 运动神经元尚不清楚。通过对从新生雌性大鼠分离的脊髓切片进行全细胞膜片钳记录，研究了标记有染料的 URS 运动神经元的特性。如先前对成年括约肌运动神经元的研究表明，新生 URS 运动神经元比其他脊髓α运动神经元更去极化，具有更高的输入电阻。这些独特的特性使 URS 运动神经元比其他α运动神经元更具兴奋性。此外，NA 的浴液应用可显著去极化 URS 运动神经元，并在许多情况下引发动作电位。NA 还显著增加输入电阻并降低阈值。这些变化在洗涤后逆转，被α(1)-肾上腺素受体选择性拮抗剂哌唑嗪（prazosin）大部分阻断，并被α(1)-肾上腺素受体选择性激动剂苯肾上腺素（phenylephrine）模拟。此外，NA 显著降低后超极化的幅度并增加动作电位频率。动作电位频率的增加和后超极化的减少都被小电导钙激活钾（SK(Ca))通道阻断剂 apamin 阻断。总之，NA 通过多种机制有效地增加 URS 运动神经元的兴奋性。NA 对尿道横纹括约肌运动神经元兴奋性的增加可能是 NA 再摄取抑制剂改善压力性尿失禁的关键机制。
