权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

Role of regulation of membrane potential by potassium channel in rat uterine contraction

钾通道调节膜电位在大鼠子宫收缩中的作用

基本信息

批准号：
10671545
负责人：
MIVOSHI Hiroshi
金额：
$ 2.05万
依托单位：
Hiroshima University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
1998
资助国家：
日本
起止时间：
1998 至 2000
项目状态：
已结题

项目摘要

Potassium (K) currents in uterine smooth muscle cells play important roles in regulating contractility by controlling the resting membrane potential. We applied the patch clamp method to myometrial cells isolated from pregnant rat for characterization of K channel.In whole-cell method, two components of voltage-dependent K current, delayed rectifier (Kd) and transient (Kt) were observed. Kd currents have a slow inactivation process (τ>500ms) and a half-inactivation voltage (V_<1/2>) of -47 mV.Kt currents inactivated more quickly (τ<50ms) with V_<1/2>=-71 mV.The Kd current is sensitive to tetraethylammonium (TEA, IC_<50> of 5.0 mM) and indapamide but not to E-4031, indicating this channel is IKs type. This channel should reporalize the membrane potential after action potentials. Kt channel is sensitive to 4AP (2 mM) and may inhibit the generation of action potentials. In inside-out mode, large Kca channels (250 pS) were observed with an IC_<50> for intracellular Ca^<2+> of 3×10^<-6> M and detected to be maxi-K type. It is clear that Kd current is not due to Kca since 1) In inside-out mode, Kca current is very sensitive to ChTX (charybdotoxin, IC_<50>=20 nM), but in whole cell mode, 100 nM ChTX blocked Kd current by just 15%. 2) TEA was much more effective in blocking Kca than Kd. 3) Kd current was observed with 5 mM BAPTA in the intracellular solution (Ca<10^<-8>). The role of this channel should be hyperpolarization after the uterine contraction.We conclude that there are at least two types of voltage dependent K channels in addition to a Ca-activated K channel (maxi-K type) in myometrial cells. These studies contribute to an understanding of current regulation in the myometrial cell and may assist in defining strategies for the control of myometrial contractility.

子宫平滑肌细胞钾电流通过控制静息膜电位在收缩性调节中起重要作用。应用膜片钳法对妊娠大鼠子宫肌瘤细胞进行K通道表征。在全细胞方法中，观察到电压依赖性K电流的两个组成部分，延迟整流（Kd）和瞬态（Kt）。Kd电流的失活过程较慢（τ>500ms），半失活电压（V_<1/2>）为- 47mv。当V_<1/2>=-71 mV时，Kt电流灭活更快（τ<50ms）。Kd电流对四乙基铵（TEA, IC_<50>, 5.0 mM）和吲达帕胺敏感，但对E-4031不敏感，表明该通道为IKs型。该通道应在动作电位后报告膜电位。Kt通道对4AP （2mm）敏感，可能抑制动作电位的产生。在内向外模式下，观察到大的Kca通道（250 pS），细胞内Ca^<2+> （3×10^<-6> M）的IC_<50>，检测到为max - k型。很明显，Kd电流不是由Kca引起的，因为1)在内向外模式下，Kca电流对ChTX （charybdotoxin, IC_<50>=20 nM）非常敏感，但在全细胞模式下，100 nM ChTX仅阻断了15%的Kd电流。2) TEA对Kca的阻断作用比Kd更有效。3)在细胞内溶液中，5mm BAPTA可以观察到Kd电流（Ca<10^<-8>）。此通道的作用应为子宫收缩后的超极化。我们得出结论，在肌内膜细胞中，除了ca激活的K通道（max -K型）外，至少存在两种类型的电压依赖性K通道。这些研究有助于理解子宫肌层细胞的当前调控，并可能有助于确定控制子宫肌层收缩性的策略。