Lysophosphatidylcholine enhances IKs currents in cardiac myocytes through activation of G protein, PKC and Rho signaling pathways
Lysophosphatidylcholine enhances IKs currents in cardiac myocytes through activation of G protein, PKC and Rho signaling pathways
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DOI：
10.1016/j.yjmcc.2010.10.006
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发表时间：
2011-01-01
影响因子：
5
通讯作者：
Matsuura, Hiroshi
中科院分区：
文献类型：
--
作者：
Ding, Wei-Guang;Toyoda, Futoshi;Matsuura, Hiroshi
溶血磷脂酰胆碱（LPC）是一种生物活性磷脂，在缺血心肌中迅速蓄积。近年来，已经表明LPC的一些作用是通过膜G蛋白的活化介导的。然而，在心脏离子通道的调节中负责LPC相关的细胞内信号传导的精确机制仍然知之甚少。本研究旨在研究LPC是否调节延迟整流K+电流（I-KS）的慢成分，如果是，则哪些细胞内信号对该过程很重要。采用膜片钳全细胞技术对豚鼠心肌细胞进行电压钳制。1-棕榈酰-溶血磷脂酰胆碱（LPC-16）的水浴应用浓度依赖性地（EC_（50）=0-7 μ M）和可逆地增加心房细胞的I-Ks，但不能增强心室肌细胞的I-Ks。相比之下，1-油酰溶血磷脂酰胆碱（LPC-18：1）仅产生轻微的I-Ks增加，1-己酰溶血磷脂酰胆碱（LPC-6）或LPC-16前体（磷脂酰胆碱）对I-Ks没有影响。用G2 A受体N端抗体预处理心房细胞可显著降低LPC-16诱导的I-Ks增强作用。抑制异源三聚体G蛋白、磷脂酶C（PLC）和蛋白激酶C（PKC）可显著降低LPC-16诱导的I-Ks增强作用。此外，特异性抑制剂对Rho和Rho激酶的阻断也抑制LPC-16的活性。免疫组化结果显示，G2 A在心房肌细胞的质膜上有密集的分布。因此，本研究表明，LPC-16激活G蛋白（可能是G（α q））通过PLC-PKC和Rho激酶途径增强I-Ks电流。(C)2010爱思唯尔有限公司保留所有权利。
Lysophosphatidylcholine (LPC) is a bioactive phospholipid that accumulates rapidly in the ischemic myocardium. In recent years, it has been shown that some of the actions of LPC are mediated through the activation of the membrane G proteins. However, the precise mechanism(s) responsible for the LPC-related intracellular signaling in the regulation of cardiac ion channels are still poorly understood. The present study was undertaken to examine whether LPC regulates the slow component of the delayed rectifier K+ current (I-Ks) and, if so, what intracellular signals are important for this process. Isolated guinea pig cardiac myocytes were voltage-clamped using the whole-cell configuration of the patch-clamp method. The bath application of 1-palmitoyl-lysophosphatidylcholine (LPC-16) concentration-dependently (EC50=0-7 mu M) and reversibly increased I-Ks in atrial cells, but failed to potentiate I-Ks in ventricular myocytes. In contrast, 1-oleoyllysophosphatidylcholine (LPC-18:1) only produced a slight I-Ks increase, and 1-caproyl-lysophosphatidylcholine (LPC-6) or the LPC-16 precursor (phosphatidylcholine) had no effect on I-Ks. Pretreatment of atrial cells with an antibody against the N-terminus of the G2A receptor significantly reduced the LPC-16-induced potentiation of I-Ks. The inhibition of heterotrimeric G protein, phospholipase C (PLC) and protein kinase C (PKC) significantly reduced LPC-16-induced enhancement of I-Ks. Moreover, the blockade of Rho and Rho-kinase by specific inhibitors also inhibited the activity of LPC-16. Immunohistochemical studies demonstrated that G2A was densely distributed in the plasma membrane of atrial myocytes. Therefore, the present study suggests that the activation of a G protein (probably G(alpha q)) by LPC-16 potentiates I-Ks currents through the PLC-PKC and Rho-kinase pathways. (C) 2010 Elsevier Ltd. All rights reserved.