Hashitani Hikaru, Brading Alison F
University Department of Pharmacology, Mansfield Road, Oxford OX1 3QT, UK.
Br J Pharmacol. 2003 Sep;140(1):159-69. doi: 10.1038/sj.bjp.0705320. Epub 2003 Aug 11.
(1) The regulatory mechanisms of spontaneous excitation in detrusor smooth muscles of the guinea-pig urinary bladder were investigated using intracellular microelectrode and muscle tension recording techniques. (2) Detrusor smooth muscle cells exhibited nifedipine-sensitive spontaneous action potentials. Their frequency was highly sensitive to membrane polarization and was reduced by lowering the temperature. Lowering the temperature also reduced the frequency of spontaneous contractions and increased their amplitude. (3) Charybdotoxin (50 nm) and iberiotoxin (0.1 microm) increased the amplitude and duration of action potentials, and abolished after hyperpolarizations (AHPs). Both agents also increased the amplitude and duration of spontaneous contractions, and reduced their frequency. Apamin (0.1 microm) did not change the shape of action potentials but often converted individual action potentials into bursts. It also increased the amplitude and duration of spontaneous contractions, and reduced their frequency. 4-aminopyrideine (4-AP, 1 mm) increased the frequency of action potentials without affecting their shape, and increased the amplitude and frequency of spontaneous contractions. (4) Cyclopiazonic acid (CPA, 10 microm) and ryanodine (50 microm) increased the amplitude of action potentials, and suppressed AHPs. Both agents also increased the amplitude and duration of spontaneous contractions, and reduced their frequency. 1,2-(Bis (2-aminophenoxy) ethane-N,N,N', N'-tetraacetic acid tetrakis (acetoxymethyl ester) (50 microm) dramatically increased the amplitude and duration of the action potential, and abolished AHPs. (5) Spontaneous action potentials in detrusor smooth muscles cells result from the opening of L-type Ca2+ channels, and their frequency is regulated by voltage-dependent mechanisms and by some metabolic process. Both the activation of large conductance Ca2+-activated K+ (BK) channels and Ca2+-mediated inactivation of the Ca2+ channels are involved in the repolarizing phase of action potentials. The Ca2+ influx through L-type Ca2+ channels triggers calcium-induced calcium release via ryanodine receptors and activates BK channels to generate AHPs. Both small conductance Ca2+-activated K+ channels and voltage-sensitive K+ channels may contribute to the resting membrane potential and regulate the frequency of action potentials. The regulatory mechanisms of action potentials are closely related to the regulation of spontaneous contractions.
(1) 采用细胞内微电极和肌肉张力记录技术，研究了豚鼠膀胱逼尿肌自发性兴奋的调节机制。(2) 逼尿肌平滑肌细胞表现出对硝苯地平敏感的自发性动作电位。其频率对膜极化高度敏感，且随着温度降低而降低。降低温度还会降低自发性收缩的频率并增加其幅度。(3) 大蝎毒素（50纳米）和iberiotoxin（0.1微米）增加了动作电位的幅度和持续时间，并消除了超极化后电位（AHPs）。这两种药物还增加了自发性收缩的幅度和持续时间，并降低了其频率。蜂毒明肽（0.1微米）没有改变动作电位的形状，但常常将单个动作电位转变为爆发性发放。它还增加了自发性收缩的幅度和持续时间，并降低了其频率。4-氨基吡啶（4-AP，1毫摩尔）增加了动作电位的频率而不影响其形状，并增加了自发性收缩的幅度和频率。(4) 环匹阿尼酸（CPA，10微米）和ryanodine（50微米）增加了动作电位的幅度，并抑制了AHPs。这两种药物还增加了自发性收缩的幅度和持续时间，并降低了其频率。1,2-双（2-氨基苯氧基）乙烷-N,N,N',N'-四乙酸四（乙酰氧基甲基酯）（50微米）显著增加了动作电位的幅度和持续时间，并消除了AHPs。(5) 逼尿肌平滑肌细胞中的自发性动作电位源于L型Ca2+通道的开放，其频率受电压依赖性机制和一些代谢过程的调节。大电导Ca2+激活K+（BK）通道的激活和Ca2+通道的Ca2+介导失活都参与了动作电位的复极化阶段。通过L型Ca2+通道的Ca2+内流通过ryanodine受体触发钙诱导的钙释放，并激活BK通道以产生AHPs。小电导Ca2+激活K+通道和电压敏感性K+通道都可能有助于静息膜电位并调节动作电位的频率。动作电位的调节机制与自发性收缩的调节密切相关。
