Sui Gui-Ping, Wu Changhao, Severs Nicholas, Newgreen Donald, Fry Christopher H
The Institute of Urology, University College London, UK.
BJU Int. 2007 Feb;99(2):436-41. doi: 10.1111/j.1464-410X.2006.06568.x. Epub 2006 Oct 9.
To determine if bladder overactivity in humans is associated with an altered activity of Ca(2+) channels in detrusor smooth muscle and the consequent activation of other ion channels.
Samples of bladder were obtained from patients with urodynamically stable bladders, or with idiopathic detrusor overactivity. Isolated cells were patch-clamped with pipettes containing a Cs(+)-based filling solution to isolate inward currents, or a K(+)-filling solution to measure outward current. Components of inward current were separated according to their sensitivity to NiCl(2) (< or =100 microm) and nifedipine.
Ni(2+)-sensitive (T-type) and nifedipine-sensitive (L-type) current was recorded in all cells. The voltage- and time-dependent properties were similar in cells from both patient groups. However, the current density of the L-type current was less, and that of the T-type current was greater, in myocytes from overactive bladders. In cells from overactive bladders, the mean K(+) current over the range - 80 to - 50 mV was also higher than in control cells. This current was sensitive to the large-conductance channel modulator iberiotoxin and to NiCl(2) (100 microm)
Detrusor myocytes from overactive human bladders have a higher T-type Ca(2+) current density; we propose that this increases transient outward currents, and so might contribute to higher levels of spontaneous activity.
确定人类膀胱过度活动症是否与逼尿肌平滑肌中Ca(2+)通道活性改变以及其他离子通道的后续激活有关。
从尿动力学稳定的膀胱患者或特发性逼尿肌过度活动症患者获取膀胱样本。使用含有基于Cs(+)的灌流液的移液管对分离出的细胞进行膜片钳记录以分离内向电流，或使用含K(+)的灌流液来测量外向电流。根据内向电流对NiCl(2)（≤100微摩尔）和硝苯地平的敏感性分离其成分。
在所有细胞中均记录到了对Ni(2+)敏感的（T型）电流和对硝苯地平敏感的（L型）电流。两组患者细胞的电压和时间依赖性特性相似。然而，过度活动膀胱的肌细胞中L型电流的电流密度较小，而T型电流的电流密度较大。在过度活动膀胱的细胞中，-80至-50 mV范围内的平均K(+)电流也高于对照细胞。该电流对大电导通道调节剂iberiotoxin和NiCl(2)（100微摩尔）敏感。
过度活动的人类膀胱的逼尿肌肌细胞具有较高的T型Ca(2+)电流密度；我们认为这会增加瞬时外向电流，因此可能导致更高水平的自发活动。
