BKCa channel activation by membrane-associated cGMP kinase may contribute to uterine quiescence in pregnancy
BKCa channel activation by membrane-associated cGMP kinase may contribute to uterine quiescence in pregnancy
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DOI：
10.1152/ajpcell.2000.279.6.c1751
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发表时间：
2000-12-01
影响因子：
5.5
通讯作者：
Korth, M
中科院分区：
文献类型：
--
作者：
Zhou, XB;Wang, GX;Korth, M
我们研究了妊娠对大电导钙激活钾通道（BKCa）活性（NPo）和离体人子宫肌层平滑肌细胞膜通道表达的影响。妊娠子宫肌层（PM）内面朝外斑的NPo高于非妊娠子宫肌层（NPM），并且半最大激活电位向更负的电位移动了39 mV。这种作用不是由于BKCa通道表达增强。在cAMP激酶（PKA）或cGMP激酶（PKG）存在下，PM斑的NPo增加，而NPM斑的NPo减少。蛋白质印迹分析和使用特定的PKG抑制剂（1 μ M KT-5823）验证了部分活性膜相关PKG的存在。PKA的抑制肽PKI抑制PKA对NPo无影响。来自PM的8-对氯苯硫基-cGMP（8-pCPT-cGMP）超极化细胞。这种作用被iberiotoxin（一种BKCa通道的特异性阻断剂）消除。它的结论是，一个内源性的，膜结合PKG在子宫肌层细胞特异性增强BKCa通道活性在怀孕期间，因此可能有助于子宫静止在怀孕期间。
We investigated the influence of pregnancy on large-conductance calcium-activated potassium channel (BKCa) activity (NPo) and on channel expression in membranes of isolated human myometrial smooth muscle cells. NPo in inside-out patches was higher in pregnant myometria (PM) compared with nonpregnant myometria (NPM), and the half-maximal activation potential was shifted by 39 mV to more negative potentials. This effect was not due to an enhanced BKCa channel expression. In the presence of cAMP kinase (PKA) or cGMP kinase (PKG), NPo increased in patches from PM but decreased in those from NPM. Western blot analysis and use of a specific PKG inhibitor (1 muM KT-5823) verified the existence of a partially active membrane-associated PKG. Inhibition of PKA by 100 nM PKI, the inhibitory peptide of PKA, had no effect on NPo. 8-p-Chlorophenylthio-cGMP (8-pCPT-cGMP) hyperpolarized cells from PM. This effect was abolished by iberiotoxin, a specific blocker of BKCa channels. It is concluded that an endogenous, membrane-bound PKG in myometrial cells specifically enhances BKCa channel activity during pregnancy and thus may contribute to uterine quiescence during pregnancy.