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首页> 外文期刊>Physiological Research >A Role for Receptor-Operated Ca2+ Entry in Human Pulmonary Artery Smooth Muscle Cells in Response to Hypoxia
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A Role for Receptor-Operated Ca2+ Entry in Human Pulmonary Artery Smooth Muscle Cells in Response to Hypoxia

机译：缺氧反应中人肺动脉平滑肌细胞中受体操纵的Ca2 +进入的作用

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Hypoxic pulmonary vasoconstriction (HPV) is an important homeostatic mechanism in which increases of [Ca~(2+)]_i are primary events. In this study, primary cultured, human pulmonary artery smooth muscle cells (hPASMC) were used to examine the role of TRPC channels in mediating [Ca~(2+)]_i elevations during hypoxia. Hypoxia (PO2 about 20 mm Hg) evoked a transient [Ca~(2+)]_i elevation that was reduced by removal of extracellular calcium. Nifedipine and verapamil, blockers of voltage-gated calcium channels (VGCCs), attenuated the hypoxia-induced [Ca~(2+)]_i elevation by about 30 %, suggesting the presence of alternate Ca~(2+) entry pathways. Expression of TRPC1 and TRPC6 in hPASMC were found by RT-PCR and confirmed by Western blot analysis. Antagonists for TRPC, 2APB and SKF96365, significantly reduced hypoxia-induced [Ca~(2+)]_i elevation by almost 60 %. Both TRPC6 and TRPC1 were knocked down by siRNA, the loss of TRPC6 decreased hypoxic response down to 21 % of control, whereas the knockdown of TRPC1 reduced the hypoxia response to 85 %, suggesting that TRPC6 might play a central role in mediating hypoxia response in hPASMC. However, blockade of PLC pathway caused only small inhibition of the hypoxia response. In contrast, AICAR, the agonist of AMP-activated kinase (AMPK), induced a gradual [Ca~(2+)]_i elevation, whereas compound C, an antagonist of AMPK, almost abolished the hypoxia response. However, co-immunoprecipitation revealed that AMPKα was not colocalized with TRPC6. Our data supports a role for TRPC6 in mediation of the [Ca~(2+)]_i elevation in response to hypoxia in hPASMC and suggests that this response may be linked to cellular energy status via an activation of AMPK.
机译：缺氧性肺血管收缩（HPV）是一种重要的体内平衡机制，其中[Ca〜（2 +）] _ i升高是主要事件。在这项研究中，原代培养的人类肺动脉平滑肌细胞（hPASMC）被用于检查TRPC通道在缺氧期间介导[Ca〜（2 +）] _ i升高中的作用。缺氧（PO2约20毫米汞柱）引起短暂的[Ca〜（2 +）] _ i升高，该升高通过去除细胞外钙而降低。硝苯地平和维拉帕米是电压门控钙通道（VGCC）的阻滞剂，可将缺氧诱导的[Ca〜（2 +）] _ i升高降低约30％，表明存在替代的Ca〜（2+）进入途径。通过RT-PCR发现hPASMC中TRPC1和TRPC6的表达，并通过Western印迹分析证实。 TRPC，2APB和SKF96365的拮抗剂可将缺氧诱导的[Ca〜（2 +）] _ i升高显着降低近60％。 siRNA敲低了TRPC6和TRPC1，失去TRPC6降低了低氧反应至对照组的21％，而敲低TRPC1将缺氧反应降低至85％，这表明TRPC6可能在介导低氧反应中起重要作用。 hPASMC。但是，PLC途径的阻断仅引起低氧反应的少量抑制。相反，AMP激活激酶（AMPK）的激动剂AICAR引起[Ca〜（2 +）] _ i逐渐升高，而AMPK的拮抗剂化合物C几乎消除了低氧反应。但是，共免疫沉淀显示AMPKα与TRPC6不共定位。我们的数据支持TRPC6在hPASMC缺氧反应中介导[Ca〜（2 +）] _ i升高中的作用，并表明该反应可能通过激活AMPK与细胞能量状态相关。

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