Yanai Yoshimasa, Hashitani Hikaru, Kubota Yasue, Sasaki Shoichi, Kohri Kenjiro, Suzuki Hikaru
Department of Nephro-urology, Nagoya City University Medical School, Nagoya, Japan.
BJU Int. 2006 Jan;97(1):182-9. doi: 10.1111/j.1464-410X.2006.05894.x.
To explore the role of Ni(2+)-sensitive T-type Ca(2+) channels in the generation of spontaneous excitation of detrusor smooth muscles.
In isolated detrusor smooth muscle bundles of the guinea-pig bladder, changes in the membrane potential and muscle tension were measured using intracellular microelectrodes and isometric tension recording. Changes in the intracellular Ca(2+) concentration were recorded from bundles loaded with the fluorescent dye fura-PE3.
Detrusor smooth muscles had two types of spontaneous electrical activity, i.e. individual and bursting action potentials. Ni(2+) (30 microM), a blocker for T-type Ca(2+) channels, reduced the frequency of individual action potentials without changing their amplitude. Higher concentrations of Ni(2+) (100-300 microM) converted individual action potentials into the bursts, as did apamin (0.1 microM), a blocker of small-conductance Ca(2+)-activated K(+) channels (SK). They also increased the amplitudes of spontaneous Ca(2+) transients and corresponding contractions whilst reducing their frequencies. In preparations which generated bursting action potentials, nifedipine (1 microm) converted action potentials into spontaneous transient depolarizations (STDs), and subsequent applications of Ni(2+) (100 microm) abolished STDs. Gadolinium (100 microM) and SKF96365 (10 microM), blockers for nonselective cation channels, and niflumic acid (100 microm), a blocker for Ca(2+)-activated Cl- channels, had no effect on either the amplitude or frequency of spontaneous action potentials.
The T-type Ca(2+) channel may have dual roles in generating spontaneous excitation in detrusor smooth muscles. First, activity of these channels may account for the preceding depolarizations that lead to action potentials. Second, Ca(2+) influx through T-type Ca(2+) channels may couple functionally to SK channels, contributing to the stability of the resting membrane potential in detrusor smooth muscle. Thus, pharmacological manipulation of T-type Ca(2+) channels in detrusor smooth muscles could be of potential value for treating the overactive bladder.
探讨镍离子敏感的T型钙通道在逼尿肌平滑肌自发兴奋产生中的作用。
在豚鼠膀胱分离的逼尿肌平滑肌束中，使用细胞内微电极和等长张力记录法测量膜电位和肌肉张力的变化。从加载荧光染料fura-PE3的肌束记录细胞内钙离子浓度的变化。
逼尿肌平滑肌有两种自发电活动类型，即单个动作电位和爆发性动作电位。T型钙通道阻滞剂镍离子（30微摩尔）降低单个动作电位的频率但不改变其幅度。更高浓度的镍离子（100 - 300微摩尔）将单个动作电位转变为爆发性动作电位，小电导钙激活钾通道（SK）阻滞剂蜂毒明肽（0.1微摩尔）也有同样作用。它们还增加自发钙瞬变和相应收缩的幅度，同时降低其频率。在产生爆发性动作电位的标本中，硝苯地平（1微摩尔）将动作电位转变为自发瞬时去极化（STD），随后应用镍离子（100微摩尔）可消除STD。非选择性阳离子通道阻滞剂钆（100微摩尔）和SKF96365（10微摩尔）以及钙激活氯通道阻滞剂氟灭酸（100微摩尔）对自发动作电位的幅度或频率均无影响。
T型钙通道在逼尿肌平滑肌产生自发兴奋中可能具有双重作用。首先，这些通道的活动可能是导致动作电位的先前去极化的原因。其次，通过T型钙通道的钙内流可能在功能上与SK通道偶联，有助于逼尿肌平滑肌静息膜电位的稳定性。因此，对逼尿肌平滑肌中T型钙通道进行药理学调控可能对治疗膀胱过度活动症具有潜在价值。
