首页> 外文期刊>American Journal of Physiology >PKC activates BKCa channels in rat pulmonary arterial smooth muscle via cGMP-dependent protein kinase.
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PKC activates BKCa channels in rat pulmonary arterial smooth muscle via cGMP-dependent protein kinase.

机译:PKC通过cGMP依赖性蛋白激酶激活大鼠肺动脉平滑肌中的BKCa通道。

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摘要

Normally, signaling mechanisms that activate large-conductance, calcium- and voltage-activated potassium (BK(Ca)) channels in pulmonary vascular smooth muscle cause pulmonary vasodilatation. BK(Ca)-channel modulation is important in the regulation of pulmonary arterial pressure, and inhibition (decrease in the opening probability) of the BK(Ca) channel has been implicated in the development of pulmonary vasoconstriction. Protein kinase C (PKC) causes pulmonary vasoconstriction, but little is known about the effect of PKC on BK(Ca)-channel activity in pulmonary vascular smooth muscle. Accordingly, studies were done to determine the effect of PKC on BK(Ca)-channel activity using patch-clamp studies in pulmonary arterial smooth muscle cells (PASMCs) of the Sprague-Dawley rat. The PKC activators phorbol myristate acetate (PMA) and thymeleatoxin opened BK(Ca) channels in single Sprague-Dawley rat PASMC. The activator response to both PMA and thymeleatoxin on BK(Ca)-channel activity was blocked by Go-6983, which selectively blocks PKC-alpha, -delta, -gamma, and -zeta, and by rottlerin, which selectively inhibits PKC-delta. In addition, the specific cyclic GMP-dependent protein kinase antagonist KT-5823 blocked the responses to PMA and thymelatoxin, whereas the specific cyclic AMP-dependent protein kinase blocker KT-5720 had no effect. In isolated pulmonary arterial vessels, both PMA and forskolin caused vasodilatation, which was inhibited by KT-5823, Go-6983, or the BK(Ca)-channel blocker tetraethylammonium. The results of this study indicate that activation of specific PKC isozymes increases BK(Ca)-channel activity in Sprague-Dawley rat PASMC via cyclic GMP-dependent protein kinase, which suggests a unique signaling mechanism for vasodilatation.
机译:通常,激活肺血管平滑肌中大电导,钙和电压激活的钾(BK(Ca))通道的信号传导机制会引起肺血管扩张。 BK(Ca)通道调制在肺动脉压的调节中很重要,并且BK(Ca)通道的抑制(打开概率的降低)与肺血管收缩的发展有关。蛋白激酶C(PKC)引起肺血管收缩,但关于PKC对肺血管平滑肌BK(Ca)通道活性的影响知之甚少。因此,进行了研究以确定在Sprague-Dawley大鼠的肺动脉平滑肌细胞(PASMC)中使用膜片钳研究PKC对BK(Ca)通道活性的影响。 PKC激活剂佛波醇肉豆蔻酸酯乙酸(PMA)和百里香酚毒素在单个Sprague-Dawley大鼠PASMC中打开BK(Ca)通道。激活剂对PMA和胸腺毒素对BK(Ca)通道活性的响应被Go-6983(有选择地阻断PKC-α,-δ,-γ和-zeta)和rottlerin(有选择地抑制PKC-δ)阻断。 。此外,特定的环状GMP依赖性蛋白激酶拮抗剂KT-5823阻断了对PMA和胸腺毒素的反应,而特定的环状AMP依赖性蛋白激酶阻断剂KT-5720没有作用。在孤立的肺动脉血管中,PMA和福司可林都引起血管扩张,这被KT-5823,Go-6983或BK(Ca)通道阻滞剂四乙铵抑制。这项研究的结果表明,特定的PKC同工酶的激活通过环状GMP依赖性蛋白激酶增加了Sprague-Dawley大鼠PASMC中的BK(Ca)通道活性,这提示了血管舒张的独特信号传导机制。

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