Selective activation of adrenoceptors potentiates IKs current in pulmonary vein cardiomyocytes through the protein kinase A and C signaling pathways
Selective activation of adrenoceptors potentiates IKs current in pulmonary vein cardiomyocytes through the protein kinase A and C signaling pathways
复制标题
选择性激活肾上腺素受体通过蛋白激酶 A 和 C 信号通路增强肺静脉心肌细胞中的 IK 电流
DOI：
10.1016/j.yjmcc.2021.08.004
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发表时间：
2021
影响因子：
5
通讯作者：
M. Omatsu-Kanbe and H. Matsuura
中科院分区：
文献类型：
--
作者：
X. Mi;W. G. Ding;F. Toyoda;A. Kojima;M. Omatsu-Kanbe and H. Matsuura
延迟整流钾电流(Iks)是动作电位复极的关键因素。本研究探讨了在肺静脉心肌细胞(PVC)中肾上腺素能受体诱导IKI增强的机制。从豚鼠肺静脉中分离出PVC。采用穿孔和常规全细胞膜片钳技术记录动作电位和Iks电流。免疫细胞化学和Western blotting检测到IKs的表达。KCNQ1是一条约100 kDa的信号带，其免疫荧光信号主要定位于细胞膜。刺激β_1和β_2肾上腺素能受体均可显著增强pVc的电流，但β_2肾上腺素能受体刺激比β_1肾上腺素能受体刺激更有效地引起电流负移。腺苷环化酶(AC)抑制剂或蛋白激酶A(PKA)抑制剂可减弱β-肾上腺素受体介导的IKs的升高。此外，α1肾上腺素能受体激动剂可使Iks电流增加，而蛋白激酶C抑制剂可使其减弱。聚氯乙烯在正常的Tyrode溶液中表现出动作电位，而选择性IKs阻断剂HMR-1556使其略有降低。然而，HMR-1556显著降低β-肾上腺素能受体增强的放电频率。β-和α-1-肾上腺素能受体对血管内皮细胞的刺激作用是通过PKA和PKC信号通路介导的。HMR-1556有效地降低了β-肾上腺素能受体激活下的放电频率，提示在活体条件下交感神经兴奋时，IKm的作用可能增强。
Delayed rectifier K+current (IKs) is a key contributor to repolarization of action potentials. This study investigated the mechanisms underlying the adrenoceptor-induced potentiation ofIKsin pulmonary vein cardiomyocytes (PVC). PVC were isolated from guinea pig pulmonary vein. The action potentials andIKscurrent were recorded using perforated and conventional whole-cell patch-clamp techniques. The expression ofIKswas examined using immunocytochemistry and Western blotting.KCNQ1, aIKspore-forming protein was detected as a signal band approximately 100 kDa in size, and its immunofluorescence signal was found to be mainly localized on the cell membrane. TheIKscurrent in PVC was markedly enhanced by both β1- and β2-adrenoceptor stimulation with a negative voltage shift in the current activation, although the potentiation was more effectively induced by β2-adrenoceptor stimulation than β1-adrenoceptor stimulation. Both β-adrenoceptor-mediated increases inIKswere attenuated by treatment with the adenylyl cyclase (AC) inhibitor or protein kinase A (PKA) inhibitor. Furthermore, theIKscurrent was increased by α1-adrenoceptor agonist but attenuated by the protein kinase C (PKC) inhibitor. PVC exhibited action potentials in normal Tyrode solution which was slightly reduced by HMR-1556 a selectiveIKsblocker. However, HMR-1556 markedly reduced the β-adrenoceptor-potentiated firing rate. The stimulatory effects of β- and α1-adrenoceptor onIKsin PVC are mediated via the PKA and PKC signal pathways. HMR-1556 effectively reduced the firing rate under β-adrenoceptor activation, suggesting that the functional role ofIKsmight increase during sympathetic excitation underin vivoconditions.