Angiotensin II-stimulated Ca2+ entry mechanisms in afferent arterioles:: role of transient receptor potential canonical channels and reverse Na+/Ca2+ exchange
Angiotensin II-stimulated Ca2+ entry mechanisms in afferent arterioles:: role of transient receptor potential canonical channels and reverse Na+/Ca2+ exchange
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DOI：
10.1152/ajprenal.00244.2007
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发表时间：
2008-01-01
影响因子：
4.2
通讯作者：
Arendshorst, William J.
中科院分区：
文献类型：
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作者：
Fellner, Susan K.;Arendshorst, William J.
在传入小动脉中，导致胞质Ca 2+浓度（[Ca 2 +]（i））增加和血管收缩启动的信号事件越来越多地被描绘出来。我们最近研究了血管紧张素II（ANG II）介导的影响肌浆网（SR）动员的钙离子和超氧化物和环腺苷二磷酸核糖在这些过程中的作用。在本研究中，我们研究了瞬时受体电位典型通道（TRPC）和Na+/Ca 2+交换器（NCX）在Ca 2+内流机制中的参与。用磁化聚苯乙烯珠法分离传入小动脉，用Fura-2负载以比率计量法测量[Ca 2 +]（i）。我们观察到，钙离子依赖性氯离子通道阻滞剂尼氟灭酸（10和50 μ M）既不影响峰值也不影响平台[Ca 2 +]（i）对ANG II的反应。用兰尼碱（100 μ M）和TMB-8预处理小动脉，分别通过兰尼碱受体和三磷酸肌醇受体阻断SR动员。2-氨基乙氧基二苯硼烷阻断TRPC介导的钙内流可使ANG Ⅱ的[Ca 2 +]（i）峰降低80%，平台降低74%。氟芬那酸（FFA; 50 μ M），刺激TRPC 6，导致[Ca 2 +]（i）持续增加146 nM。这种反应不受地尔硫卓或硝苯地平的影响。KB-R7943（在10 μ M的低浓度下）抑制反向（但不正向）模式NCX。KB-R7943使对ANG II的峰值[Ca ~（2+）]（i）反应降低48%，使对FFA的峰值[Ca ~（2+）]（i）反应降低38%。我们的结论是，TRPC 6和反向模式NCX可能是重要的Ca 2+进入途径在传入小动脉。
In afferent arterioles, the signaling events that lead to an increase in cytosolic Ca2+ concentration ([Ca2+](i)) and initiation of vascular contraction are increasingly being delineated. We have recently studied angiotensin II (ANG II)-mediated effects on sarcoplasmic reticulum (SR) mobilization of Ca2+ and the role of superoxide and cyclic adenosine diphosphoribose in these processes. In the current study we investigated the participation of transient receptor potential canonical channels (TRPC) and a Na+/Ca2+ exchanger (NCX) in Ca2+ entry mechanisms. Afferent arterioles, isolated with the magnetized polystyrene bead method, were loaded with fura-2 to measure [Ca2+](i) ratiometrically. We observed that the Ca2+-dependent chloride channel blocker niflumic acid (10 and 50 mu M) affects neither the peak nor plateau [Ca2+](i) response to ANG II. Arterioles were pretreated with ryanodine (100 mu M) and TMB-8 to block SR mobilization via the ryanodine receptor and inositol trisphosphate receptor, respectively. The peak [Ca2+](i) response to ANG II was reduced by 40%.Addition of 2-aminoethoxydiphenyl borane to block TRPC-mediated Ca2+ entry inhibited the peak [Ca2+](i) ANG II response by 80% and the plateau by 74%. Flufenamic acid (FFA; 50 mu M), which stimulates TRPC6, caused a sustained increase of [Ca2+](i) of 146 nM. This response was unaffected by diltiazem or nifedipine. KB-R7943 (at the low concentration of 10 mu M) inhibits reverse (but not forward) mode NCX. KB- R7943 decreased the peak [Ca2+](i) response to ANG II by 48% and to FFA by 38%. We conclude that TRPC6 and reverse-mode NCX may be important Ca2+ entry pathways in afferent arterioles.