KCNQ currents and their contribution to resting membrane potential and the excitability of interstitial cells of Cajal from the guinea pig bladder.
KCNQ currents and their contribution to resting membrane potential and the excitability of interstitial cells of Cajal from the guinea pig bladder.
复制标题
DOI：
10.1016/j.juro.2009.02.108
复制
发表时间：
2009-07
期刊：
影响因子：
--
通讯作者：
McCloskey KD
中科院分区：
文献类型：
--
作者：
Anderson UA;Carson C;McCloskey KD
在豚鼠膀胱Cajal间质细胞中研究了新型KCNQ电流的存在，并评估了其对静息膜电位维持的贡献。采用电压钳和电流钳模式，用充钾移液管对酶分散的Cajal间质细胞进行膜片钳。对KCNQ通道的药理学调节剂进行了膜电流和静息膜电位测试。使用含有乙二醇四乙酸（5 mM）和三磷酸腺苷（3 mM）的改良K+移液器溶液将细胞从-60 mV步进至40 mV，以激发电压依赖性电流，以消除大电导Ca激活的K通道和K三磷酸腺苷电流。应用KCNQ阻断剂XE 991、linopirdine（Tocris Bioscience，Ellisville，密苏里州）和色原烷醇293 B（Sigma®）以浓度依赖性方式降低外向电流。XE 991敏感电流的电流-电压关系显示了电压依赖性的向外整流电流，该电流在−60 mV时激活，几乎没有失活。KCNQ开放剂氟吡汀和甲氨酰胺酸（Sigma）在电压范围内增加外向电流。在电流钳模式下，XE 991或色原烷醇293 B降低了Cajal间质细胞静息膜电位，并在其他静止细胞中引起自发性瞬时去极化。氟吡汀或甲桂胺酸使Cajal间质细胞超极化，并抑制任何自发电活动。本研究为膀胱Cajal间质细胞具有KCNQ电流提供了电生理学证据，KCNQ电流在调节Cajal间质细胞静息膜电位和兴奋性中起作用。这些新的发现提供了关于Cajal膀胱间质细胞中存在的离子通道的关键信息，它们可能为膀胱不稳定的新疗法的开发提供相关靶点。
The presence of novel KCNQ currents was investigated in guinea pig bladder interstitial cells of Cajal and their contribution to the maintenance of the resting membrane potential was assessed. Enzymatically dispersed interstitial cells of Cajal were patch clamped with K+ filled pipettes in voltage clamp and current clamp modes. Pharmacological modulators of KCNQ channels were tested on membrane currents and the resting membrane potential. Cells were stepped from −60 to 40 mV to evoke voltage dependent currents using a modified K+ pipette solution containing ethylene glycol tetraacetic acid (5 mM) and adenosine triphosphate (3 mM) to eliminate large conductance Ca activated K channel and Kadenosine triphosphate currents. Application of the KCNQ blockers XE991, linopirdine (Tocris Bioscience, Ellisville, Missouri) and chromanol 293B (Sigma®) decreased the outward current in concentration dependent fashion. The current-voltage relationship of XE991 sensitive current revealed a voltage dependent, outwardly rectifying current that activated positive to −60 mV and showed little inactivation. The KCNQ openers flupirtine and meclofenamic acid (Sigma) increased outward currents across the voltage range. In current clamp mode XE991 or chromanol 293B decreased interstitial cell of Cajal resting membrane potential and elicited the firing of spontaneous transient depolarizations in otherwise quiescent cells. Flupirtine or meclofenamic acid hyperpolarized interstitial cells of Cajal and inhibited any spontaneous electrical activity. This study provides electrophysiological evidence that bladder interstitial cells of Cajal have KCNQ currents with a role in the regulation of interstitial cell of Cajal resting membrane potential and excitability. These novel findings provide key information on the ion channels present in bladder interstitial cells of Cajal and they may indicate relevant targets for the development of new therapies for bladder instability.
登录
查看更多内容
影响因子：
4.2
作者：
Johnston, Louise;Carson, Chris;Lyons, Alan D.;Davidson, Ross A.;McCloskey, Karen D.
通讯作者：
McCloskey, Karen D.
影响因子：
30.8
作者：
Wang, Q;Curran, ME;Keating, MT
通讯作者：
Keating, MT
影响因子：
5.5
作者：
Wladyka, Cynthia L.;Kunze, Diana L.
通讯作者：
Kunze, Diana L.
影响因子：
5.8
作者：
Joshi, S;Balan, P;Gurney, AM
通讯作者：
Gurney, AM
影响因子：
3.4
作者：
Lamas, JA;Selyanko, AA;Brown, DA
通讯作者：
Brown, DA