Cholinergic-induced Ca2+ signaling in interstitial cells of Cajal from the guinea pig bladder.
Cholinergic-induced Ca2+ signaling in interstitial cells of Cajal from the guinea pig bladder.
复制标题
DOI：
10.1152/ajprenal.00526.2007
复制
发表时间：
2008-03
影响因子：
4.2
通讯作者：
McCloskey, Karen D.
中科院分区：
文献类型：
--
作者：
Johnston, Louise;Carson, Chris;Lyons, Alan D.;Davidson, Ross A.;McCloskey, Karen D.
副交感兴奋神经释放的乙酰胆碱激活逼尿肌平滑肌的收缩。用抗 c-Kit 和抗 VAChT 对豚鼠逼尿肌进行免疫组织化学标记，证明 Cajal 间质细胞 (ICC) 和胆碱能神经之间存在密切的结构关系。在负载 Ca2+ 指示剂 Fluo 4AM 的酶解细胞中研究了豚鼠膀胱逼尿肌 ICC 对乙酰胆碱类似物卡巴胆碱的反应能力。 ICC 响应卡巴胆碱 (1/10 μM) 的刺激而发射 Ca2+ 瞬变。它们的药理学与卡巴胆碱诱导的逼尿肌条收缩一致，该收缩被 M3 受体拮抗剂 4-DAMP (1 μM) 抑制，但不被 M2 受体拮抗剂甲氧曲明 (methoctramine) (1 μM) 抑制。使用干扰细胞内储存流入或释放的试剂，研究了分离 ICC 中卡巴胆碱瞬变背后的 Ca2+ 来源。硝苯地平 (1 μM) 或 Ni2+ (30–100 μM) 阻断 Ca2+ 通道或去除外部 Ca2+ 可降低卡巴胆碱瞬变的幅度。使用兰尼定 (30 μM) 或丁卡因 (100 μM) 可消除瞬态。磷脂酶 C 抑制剂 U-73122 (2.5 μM) 显着降低了反应。 2-氨基乙氧基二乙基硼酸酯 (30 μM) 导致显着降低，而 Xestospongin C (1 μM) 更有效，几乎消除了反应。负载 Ca2+ 指示剂的豚鼠膀胱的完整原位制备物显示平滑肌细胞和 ICC 中自发 Ca2+ 事件的明显不同模式。两种细胞类型都通过增加这些事件的频率来响应卡巴胆碱。总之，豚鼠膀胱逼尿肌 ICC，无论是作为分离的细胞还是在整个组织制剂中，都通过发射 Ca2+ 瞬变来响应胆碱能刺激。
Acetylcholine released from parasympathetic excitatory nerves activates contraction in detrusor smooth muscle. Immunohistochemical labeling of guinea pig detrusor with anti-c-Kit and anti-VAChT demonstrated a close structural relationship between interstitial cells of Cajal (ICC) and cholinergic nerves. The ability of guinea pig bladder detrusor ICC to respond to the acetylcholine analog, carbachol, was investigated in enzymatically dissociated cells, loaded with the Ca2+ indicator fluo 4AM. ICC fired Ca2+ transients in response to stimulation by carbachol (1/10 μM). Their pharmacology was consistent with carbachol-induced contractions in strips of detrusor which were inhibited by 4-DAMP (1 μM), an M3 receptor antagonist, but not by the M2 receptor antagonist methoctramine (1 μM). The source of Ca2+ underlying the carbachol transients in isolated ICC was investigated using agents to interfere with influx or release from intracellular stores. Nifedipine (1 μM) or Ni2+ (30–100 μM) to block Ca2+ channels or the removal of external Ca2+ reduced the amplitude of the carbachol transients. Application of ryanodine (30 μM) or tetracaine (100 μM) abolished the transients. The phospholipase C inhibitor, U-73122 (2.5 μM), significantly reduced the responses. 2-Aminoethoxydiethylborate (30 μM) caused a significant reduction and Xestospongin C (1 μM) was more effective, almost abolishing the responses. Intact in situ preparations of guinea pig bladder loaded with a Ca2+ indicator showed distinctively different patterns of spontaneous Ca2+ events in smooth muscle cells and ICC. Both cell types responded to carbachol by an increase in frequency of these events. In conclusion, guinea pig bladder detrusor ICC, both as isolated cells and within whole tissue preparations, respond to cholinergic stimulation by firing Ca2+ transients.
登录
查看更多内容
影响因子：
5.5
作者：
White, C;McGeown, JG
通讯作者：
McGeown, JG
影响因子：
4.5
作者：
McCloskey, KD
通讯作者：
McCloskey, KD
影响因子：
29.4
作者：
Sanders, KM
通讯作者：
Sanders, KM
影响因子：
6.6
作者：
Sui, GP;Wu, C;Fry, CH
通讯作者：
Fry, CH
影响因子：
5.5
作者：
Wu, C;Sui, GP;Fry, CH
通讯作者：
Fry, CH