Voltage dependent potassium channel remodeling in murine intestinal smooth muscle hypertrophy induced by partial obstruction.
Voltage dependent potassium channel remodeling in murine intestinal smooth muscle hypertrophy induced by partial obstruction.
复制标题
部分梗阻引起的小鼠小肠平滑肌肥大中电压依赖性钾通道重塑
DOI：
10.1371/journal.pone.0086109
复制
发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Xu WX
中科院分区：
文献类型：
--
作者：
Liu DH;Huang X;Guo X;Meng XM;Wu YS;Lu HL;Zhang CM;Kim YC;Xu WX
小肠的部分梗阻会导致梗阻附近肠道的平滑肌细胞明显肥大和动力障碍。为探讨部分梗阻后肥大小肠平滑肌的电重构，本研究采用膜片钳和细胞内微电极记录方法，并采用Western blot、免疫荧光和免疫沉淀法检测通道蛋白表达和磷酸化水平的变化。梗阻14天后，部分梗阻引起近端肠平滑肌明显肥大。与正常和假手术组相比，扩张区肠平滑肌慢波明显抑制，振幅和频率降低，静息膜电位去极化。肥大平滑肌细胞的电压依赖性钾通道（KV）电流密度显著降低，KV激活的电压敏感性改变。非选择性钾通道阻断剂TEA使KV电流（IKV）的敏感性显著增加，但对KV阻断剂4-AP的敏感性保持不变。在肥大的平滑肌细胞膜上，KV4.3和KV2.2的蛋白水平上调。在肥大的平滑肌细胞中，KV4.3和KV2.2的丝氨酸和苏氨酸磷酸化水平显著增加。因此，本研究代表了第一次确定KV通道重塑小鼠小肠平滑肌肥大引起的部分梗阻。KV4.3和KV2.2的磷酸化增强可能参与了这一过程。
Partial obstruction of the small intestine causes obvious hypertrophy of smooth muscle cells and motility disorder in the bowel proximate to the obstruction. To identify electric remodeling of hypertrophic smooth muscles in partially obstructed murine small intestine, the patch-clamp and intracellular microelectrode recording methods were used to identify the possible electric remodeling and Western blot, immunofluorescence and immunoprecipitation were utilized to examine the channel protein expression and phosphorylation level changes in this research. After 14 days of obstruction, partial obstruction caused obvious smooth muscle hypertrophy in the proximally located intestine. The slow waves of intestinal smooth muscles in the dilated region were significantly suppressed, their amplitude and frequency were reduced, whilst the resting membrane potentials were depolarized compared with normal and sham animals. The current density of voltage dependent potassium channel (KV) was significantly decreased in the hypertrophic smooth muscle cells and the voltage sensitivity of KV activation was altered. The sensitivity of KV currents (IKV) to TEA, a nonselective potassium channel blocker, increased significantly, but the sensitivity of IKv to 4-AP, a KV blocker, stays the same. The protein levels of KV4.3 and KV2.2 were up-regulated in the hypertrophic smooth muscle cell membrane. The serine and threonine phosphorylation levels of KV4.3 and KV2.2 were significantly increased in the hypertrophic smooth muscle cells. Thus this study represents the first identification of KV channel remodeling in murine small intestinal smooth muscle hypertrophy induced by partial obstruction. The enhanced phosphorylations of KV4.3 and KV2.2 may be involved in this process.
登录
查看更多内容
影响因子：
20.1
作者：
Dixon, JE;Shi, WM;McKinnon, D
通讯作者：
McKinnon, D
影响因子：
5.5
作者：
Amberg, GC;Koh, SD;Sanders, KM
通讯作者：
Sanders, KM
DOI：
10.1152/ajpgi.1998.274.5.g901
发表时间：
1998-05-01
影响因子：
4.5
作者：
Schmalz, F;Kinsella, J;Horowitz, B
通讯作者：
Horowitz, B
影响因子：
3.9
作者：
Mohapatra, D. P.;Park, K. -S.;Trimmer, J. S.
通讯作者：
Trimmer, J. S.
影响因子：
4.5
作者：
Kang, MH;Morsy, N;Akbarali, HI
通讯作者：
Akbarali, HI