C-type natriuretic peptide activates a non-selective cation current in acutely isolated rat cardiac fibroblasts via natriuretic peptide C receptor-mediated signalling
C-type natriuretic peptide activates a non-selective cation current in acutely isolated rat cardiac fibroblasts via natriuretic peptide C receptor-mediated signalling
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DOI：
10.1113/jphysiol.2006.120832
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发表时间：
2007-04-01
影响因子：
5.5
通讯作者：
Giles, W. R.
中科院分区：
文献类型：
--
作者：
Rose, R. A.;Hatano, N.;Giles, W. R.
在心脏中，成纤维细胞在细胞外基质的沉积中起着至关重要的作用，它们还分泌许多激素因子。尽管利钠肽包括C型利钠肽(CNP)和脑利钠肽(BNP)对心脏成纤维细胞具有抗纤维化作用，但CNP对成纤维细胞电生理的影响尚未见报道。本研究采用急性分离的成年大鼠心室成纤维细胞，在全细胞电压钳条件下观察CNP(2×10~(-8)M)的作用。CNP和利钠肽C受体(NPR-C)激动剂CANF(2×10(-8)M)显著增加外向整流性非选择性阳离子电流(NSCC)。该电流的反转电位接近0 mV。用百日咳毒素处理成纤维细胞后，CANF对NSCC的激活作用被取消，表明G(I)蛋白参与了这一过程。化合物Gd~(3+)、SKF~(96365)和2-氨基乙氧基二苯硼酸酯对钙调素激活的神经干细胞有抑制作用。定量RT-PCR分析显示，大鼠心室成纤维细胞中存在几种瞬时受体电位(TRP)通道转录本。电生理分析表明，磷脂酶C拮抗剂U73122可抑制CANF激活的NSCC。此外，CNP和CANF的作用可被1-油酰基-2-乙酰甘油类似物1-油酰基-2-乙酰甘油(OAG)模拟，而不依赖于蛋白激酶C的活性。这些是特定TRPC渠道的定义特征。更详细的分子分析证实了全长TRPC2、TRPC3和TRPC5转录本的表达。这些数据表明，CNP通过NPR-C受体作用，激活心脏成纤维细胞中至少部分由TRPC通道携带的NSCC。
In the heart, fibroblasts play an essential role in the deposition of the extracellular matrix and they also secrete a number of hormonal factors. Although natriuretic peptides, including C-type natriuretic peptide (CNP) and brain natriuretic peptide, have antifibrotic effects on cardiac fibroblasts, the effects of CNP on fibroblast electrophysiology have not been examined. In this study, acutely isolated ventricular fibroblasts from the adult rat were used to measure the effects of CNP (2 x 10(-8) M) under whole-cell voltage-clamp conditions. CNP, as well as the natriuretic peptide C receptor (NPR-C) agonist cANF (2 x 10(-8) M), significantly increased an outwardly rectifying non-selective cation current (NSCC). This current has a reversal potential near 0 mV. Activation of this NSCC by cANF was abolished by pre-treating fibroblasts with pertussis toxin, indicating the involvement of G(i) proteins. The cANF-activated NSCC was inhibited by the compounds Gd3+, SKF 96365 and 2-aminoethoxydiphenyl borate. Quantitative RT-PCR analysis of mRNA from rat ventricular fibroblasts revealed the expression of several transient receptor potential (TRP) channel transcripts. Additional electrophysiological analysis showed that U73122, a phospholipase C antagonist, inhibited the cANF-activated NSCC. Furthermore, the effects of CNP and cANF were mimicked by the diacylglycerol analogue 1-oleoyl-2-acetyl-sn-glycerol (OAG), independently of protein kinase C activity. These are defining characteristics of specific TRPC channels. More detailed molecular analysis confirmed the expression of full-length TRPC2, TRPC3 and TRPC5 transcripts. These data indicate that CNP, acting via the NPR-C receptor, activates a NSCC that is at least partially carried by TRPC channels in cardiac fibroblasts.