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Investigations into the spontaneous activity in smooth muscles of the lower urinary tract

下尿路平滑肌自发活动的研究

基本信息

批准号：
15591704
负责人：
HASHITANTI Hikaru
金额：
$ 2.3万
依托单位：
NAGOYA CITY UNIVERSITY
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2003
资助国家：
日本
起止时间：
2003 至 2004
项目状态：
已结题

项目摘要

Spontaneous increases in [Ca^<2+>]_i (Ca^<2+> transients) preferentially originated along the boundary of muscle bundles and then spread to the other boundary (Ca^<2+> waves). The synchronicity of Ca^<2+> waves across the detrusor smooth muscle bundles was disrupted by 18β-glycyrrhetinic acid or carbenoxolone, while CPA, ryanodine, xestospongin C and U-73122 had no effect. Nifedipine but not nominal Ca^<2+> free solution diminished the synchronicity of Ca^<2+> waves before preventing their generation. Staining for c-kit identified interstitial cells (IC) located along both boundaries of muscle bundles. IC were more dominantly distributed in connective tissue between muscle bundles. IC generated nifedipine-resistant spontaneous Ca^<2+> transients, which occurred independently of those of smooth muscles. In conclusion, the propagation of Ca^<2+> transients in the bladder appears to be exclusively mediated by the spread of action potentials through gap junctions being facilitated by the r … More egenerative nature of L-type Ca^<2+> channels, without significant contribution of intracellular Ca^<2+> stores. IC in the bladder may modulate the transmission of Ca^<2+> transients originating from smooth muscle cells rather than being the pacemaker of spontaneous activity.To investigate the cellular mechanisms underlying spontaneous excitation of smooth muscle of the guinea-pig urinary bladder, isometric tension was measured in muscle bundles while recording the membrane potential from a cell in the bundle with a microelectrode. Changes in the intracellular calcium concentration [Ca^<2+>]_i (Ca^<2+> transients) were recorded in strips loaded with the fluorescent dye. Carbachol increased the frequency of action potentials and corresponding contractions. Apamin potentiated bursting activity and enhanced phasic contraction. Charybdotoxin induced prolonged action potentials that generated enlarged contractions. In contrast, levcromakalim reduced the frequency of action potentials, action potential bursts and the size of the contractions. Forskolin, 8-bromoguanosin 3', 5' cyclic monophosphate and Y-26763 suppressed contractions without reducing the amplitude of either action potentials or Ca^<2+> transients. These results confirm that action potentials and associated calcium transients are fundamental mechanisms in generating spontaneous contractions in smooth muscles of the guinea-pig bladder. However, in parallel with the excitation-contraction coupling, the sensitivity of the contractile proteins for Ca^<2+> may play an important role in regulating spontaneous excitation and can be modulated by cyclic nucleotides and Rho kinase. Less

自发性[Ca^<2+>] i增加（Ca^<2+>瞬变）优先沿肌束边界沿着发生，然后向另一边界扩散（Ca^<2+>波）。18β-大黄酸或甘珀酸可阻断逼尿肌肌束Ca^2+波的同步性，而CPA、ryanodine、xestospongin C和U-73122则无此作用。硝苯地平而不是名义上的无Ca^2+溶液在阻止Ca^2+波的产生之前降低了Ca^2+波的同步性。c-kit染色鉴定了位于肌束沿着两侧边界的间质细胞（IC）。IC主要分布于肌束间结缔组织。IC产生硝苯地平抵抗的自发性Ca^2+瞬变，其发生独立于平滑肌。总之，膀胱中Ca^<2+>瞬变的传播似乎是由动作电位通过间隙连接的传播介导的，而间隙连接是由钙通道介导的。 ...更多信息 L-型Ca^2+通道的再生性质，而细胞内Ca^2+储存没有显著贡献。膀胱IC可能调节平滑肌细胞Ca^2+瞬变的传递，而不是自发活动的起搏器，为了研究豚鼠膀胱平滑肌自发兴奋的细胞机制，用微电极记录肌束细胞的膜电位，同时测量肌束的等长张力。细胞内钙离子浓度[Ca^2+]_i的变化（Ca^2+瞬变）记录在加载有荧光染料的条中。卡巴胆碱增加动作电位和相应收缩的频率。Apamin增强爆发活动和增强相位收缩。Charybdotoxin诱导延长的动作电位，产生扩大收缩。相比之下，左克罗卡林降低了动作电位的频率，动作电位爆发和收缩的大小。毛喉素、8-溴鸟苷3 '，5'环一磷酸盐和Y-26763抑制收缩，但不降低动作电位或Ca^2+瞬变的幅度。这些结果证实了动作电位和相关的钙瞬变是豚鼠膀胱平滑肌产生自发收缩的基本机制。然而，与兴奋-收缩偶联平行，收缩蛋白对Ca^<2+>的敏感性可能在调节自发兴奋中起重要作用，并且可以被环核苷酸和Rho激酶调节。少