Involvement of ryanodine receptors in muscarinic receptor-mediated membrane current oscillation in urinary bladder smooth muscle
Involvement of ryanodine receptors in muscarinic receptor-mediated membrane current oscillation in urinary bladder smooth muscle
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DOI：
10.1152/ajpcell.00161.2004
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发表时间：
2005-01-01
影响因子：
5.5
通讯作者：
Brading, AF
中科院分区：
文献类型：
--
作者：
Kajioka, S;Nakayama, S;Brading, AF
排尿期间的膀胱压力由两个分量组成：初始阶段性分量和随后的持续分量。为了研究持续压力下的兴奋机制，我们记录了从猪分离的逼尿肌细胞的膜，这可以用作人类排尿的模型。拟副交感神经药物迅速引起大的瞬时内向电流，随后在其持续存在期间，观察到相对较小幅度的振荡内向电流。这两种类型的内向电流被认为是造成阶段性和持续的压力上升，分别。离子替代和通道阻断剂的应用表明，钙激活的Cl-通道负责大的瞬态和振荡内向电流。此外，在膜片吸管中包含鸟苷5 '-O-（2-硫代二磷酸）表明两种内向电流都涉及G蛋白。然而，肝素在贴片移液管和xestospongin C在洗浴溶液中的应用表明，信号传导途径以外的肌醇1，4，5-三磷酸（IP 3）在内向电流振荡，不像最初的瞬态内向电流。这种不依赖于IP 3的内向电流振荡系统需要细胞外持续的Ca 2+内流和细胞内钙库的Ca 2+释放。这两种需求可能分别是SKF-96365敏感的阳离子通道和ryanodine受体。不同Ca 2+浓度的实验表明，从细胞外间隙的Ca 2+内流起着重要的作用，在起搏的振荡节律。这两种类型的内向电流的不同机制的事实可能有助于开发例如尿失禁和残余尿量控制的临床治疗。
The urinary bladder pressure during micturition consists of two components: an initial, phasic component and a subsequent, sustained component. To investigate the excitation mechanisms underlying the sustained pressure, we recorded from membranes of isolated detrusor cells from the pig, which can be used as a model for human micturition. Parasympathomimetic agents promptly evoke a large transient inward current, and subsequently during its continuous presence, oscillating inward currents of relatively small amplitudes are observed. The two types of inward current are considered to cause the phasic and sustained pressure rises, respectively. Ionic substitution and applications of channel blockers revealed that Ca2+-activated Cl- channels were responsible for the large transient and oscillating inward currents. Furthermore, the inclusion of guanosine 5'-O-(2-thiodiphosphate) in the patch pipette indicates that both inward currents involve G proteins. However, applications of heparin in the patch pipette and of xestospongin C in the bathing solution suggest a signaling pathway other than inositol 1,4,5-trisphosphate (IP3) operating in the inward current oscillations, unlike the initial transient inward current. This IP3-independent inward current oscillation system required both sustained Ca2+ influx from the extracellular space and Ca2+ release from the intracellular stores. These two requirements are presumably SKF-96365-sensitive cation channels and ryanodine receptors, respectively. Experiments with various Ca2+ concentrations suggested that Ca2+ influx from the extracellular space plays a major role in pacing the oscillatory rhythm. The fact that distinct mechanisms underlie the two types of inward current may help in development of clinical treatments of, for example, urinary incontinence and residual urine volume control.