TRPC6 is a candidate channel involved in receptor-stimulated cation currents in A7r5 smooth muscle cells
TRPC6 is a candidate channel involved in receptor-stimulated cation currents in A7r5 smooth muscle cells
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DOI：
10.1152/ajpcell.00283.2001
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发表时间：
2002-02-01
影响因子：
5.5
通讯作者：
Plant, TD
中科院分区：
文献类型：
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作者：
Jung, S;Strotmann, R;Plant, TD
为了研究哺乳动物瞬时受体电位（TRP）通道家族（TRPC 1 -7）成员在血管收缩剂诱导的血管平滑肌细胞内钙内流中的可能作用，我们研究了A7 r5主动脉平滑肌细胞[Arg（8）]-加压素（AVP）激活的通道。AVP引起细胞内游离Ca ~（2+）浓度（[Ca ~（2+）]（i））增加，包括Ca ~（2+）释放和Ca ~（2+）内流。全细胞记录显示激活的非选择性阳离子电流与双整流电流-电压关系惊人的相似，描述了一些异源表达的TRPC亚型。电流也刺激直接激活G蛋白，以及通过激活磷脂酶C γ偶联血小板衍生生长因子受体。电流不会因储存耗尽或[Ca 2 +]（i）增加而激活。应用1-油酰基-2-乙酰基-sn-甘油刺激电流独立于蛋白激酶C，TRPC 3/6/7亚家族的特性。与TRPC 6介导的电流一样，氟芬那酯也增加了A7 r5细胞中的阳离子电流。北方杂交揭示了编码TRPC 1和TRPC 6的mRNA。因此，我们认为TRPC 6是受体刺激的A7 r5平滑肌细胞Ca 2+渗透性阳离子通道的分子组成部分。
To investigate the possible role of members of the mammalian transient receptor potential (TRP) channel family (TRPC1-7) in vasoconstrictor-induced Ca2+ entry in vascular smooth muscle cells, we studied [Arg(8)]-vasopressin (AVP)-activated channels in A7r5 aortic smooth muscle cells. AVP induced an increase in free cytosolic Ca2+ concentration ([Ca2+](i)) consisting of Ca2+ release and Ca2+ influx. Whole cell recordings revealed the activation of a nonselective cation current with a doubly rectifying current-voltage relation strikingly similar to those described for some heterologously expressed TRPC isoforms. The current was also stimulated by direct activation of G proteins as well as by activation of the phospholipase Cgamma-coupled platelet-derived growth factor receptor. Currents were not activated by store depletion or increased [Ca2+](i). Application of 1-oleoyl-2-acetyl-sn-glycerol stimulated the current independently of protein kinase C, a characteristic property of the TRPC3/6/7 subfamily. Like TRPC6-mediated currents, cation currents in A7r5 cells were increased by flufenamate. Northern hybridization revealed mRNA coding for TRPC1 and TRPC6. We therefore suggest that TRPC6 is a molecular component of receptor-stimulated Ca2+-permeable cation channels in A7r5 smooth muscle cells.