Masuda Noriyuki, Masuda Hitoshi, Matsuyoshi Hiroko, Chancellor Michael B, de Groat William C, Yoshimura Naoki
Department of Urology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 15213, USA.
Neurourol Urodyn. 2008;27(8):838-44. doi: 10.1002/nau.20563.
The role of I(h) channels at the spinal level in the control of bladder function was examined in urethane anesthetized female rats.
Bladder activity was recorded via a transurethral catheter under isovolumetric conditions or via an intravesical catheter during continuous infusion cystometry. ZD7288, a selective I(h) channel inhibitor, was administered intrathecally at L6-S1 segmental levels of the spinal cord.
Under isovolumetric conditions, intrathecal 0.3 microg of ZD7288 was inactive, whereas 1 and 3 microg abolished bladder activity for 5.6 +/- 1.8 and 20.7 +/- 3.9 min, respectively. Three micrograms also tended to decrease the amplitude of the contractions when they reappeared. During continuous cystometry, an intrathecal injection of ZD7288 at 0.3-3 microg dose-dependently increased the intercontraction intervals by 7.5%, 33.1%, and 57.5% from pre-drug values. A higher dose of ZD7288 (3 microg) tended to increase the pressure threshold for inducing micturition by 16.6% and the maximum voiding pressure by 11.1%. On the other hand, cardiovascular parameters such as heart rate and mean blood pressure were not affected by 0.3-3 microg of intrathecal ZD7288.
These results indicate that I(h) channels play an important role in the control of micturition. Because I(h) channel inhibition in the lumbosacral spinal cord reduced the frequency of the micturition reflex without significantly affecting the amplitude of reflex bladder contraction, I(h) channels might preferentially be involved in afferent processing in the spinal cord to control the micturition reflex.
在乌拉坦麻醉的雌性大鼠中研究脊髓水平的I(h)通道在膀胱功能控制中的作用。
在等容条件下通过经尿道导管记录膀胱活动，或在持续灌注膀胱测压期间通过膀胱内导管记录。选择性I(h)通道抑制剂ZD7288在脊髓L6-S1节段水平鞘内给药。
在等容条件下，鞘内注射0.3微克ZD7288无活性，而1微克和3微克分别使膀胱活动消失5.6±1.8分钟和20.7±3.9分钟。3微克在收缩再次出现时也倾向于降低收缩幅度。在持续膀胱测压期间，鞘内注射0.3 - 3微克剂量依赖性的ZD7288使收缩间期比给药前值增加7.5%、33.1%和57.5%。更高剂量的ZD7288（3微克）倾向于使诱发排尿的压力阈值增加16.6%，最大排尿压力增加11.1%。另一方面，心率和平均血压等心血管参数不受鞘内注射0.3 - 3微克ZD7288的影响。
这些结果表明I(h)通道在排尿控制中起重要作用。由于腰骶脊髓中I(h)通道的抑制降低了排尿反射频率，而对反射性膀胱收缩幅度无明显影响，I(h)通道可能优先参与脊髓传入处理以控制排尿反射。
