Heteromeric TRPV4/TRPC1 channels mediate calcium-sensing receptor-induced nitric oxide production and vasorelaxation in rabbit mesenteric arteries.
Heteromeric TRPV4/TRPC1 channels mediate calcium-sensing receptor-induced nitric oxide production and vasorelaxation in rabbit mesenteric arteries.
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DOI：
10.1016/j.vph.2017.08.005
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发表时间：
2017-09
影响因子：
4
通讯作者：
Albert AP
中科院分区：
文献类型：
--
作者：
Greenberg HZE;Carlton-Carew SRE;Khan DM;Zargaran AK;Jahan KS;Vanessa Ho WS;Albert AP
通过增加外钙浓度刺激钙敏感受体(CaSR)，通过产生一氧化氮(NO)和激活中间钙激活的钾电流(IKCa)通道来诱导内皮依赖性的血管松弛。本研究探讨了异构体TRPV4-TRPC1通道在介导CaSR诱导的血管反应中的潜在作用。免疫细胞化学和邻近连接分析表明，TRPV4和TRPC1蛋白在新鲜分离的内皮细胞的质膜上表达和共定位。在丝状肌图研究中，在1至6 mM之间增加[Ca2+]o可浓度依赖性地松弛甲氧胺(MO)诱导的预收缩张力，这可被TRPV4拮抗剂RN1734和HC067047以及外部作用的TRPC1阻断抗体T1E3抑制。此外，用荧光NO指示剂DAF-FM测定，RN1734和T1E3可减少CaSR诱导的内皮细胞中NO的产生。相反，RN1734和T1E3不影响内皮细胞[Ca~(2+)]o诱发的穿孔-斑片IKCa电流。TRPV4激动剂GSK1016790A(葛兰素史克)对内皮依赖性地松弛MO引起的预收缩张力，增加NO的产生，此作用可被一氧化氮合酶抑制剂L-NAME、RN1734和T1E3所抑制。GSK激活RN1734和T1E3阻断的内皮细胞贴壁膜上的6Ps阳离子通道活性。这些结果表明，在兔肠系膜动脉中，异构体TRPV4-TRPC1通道通过产生NO而不是激活IKCa通道来介导CaSR引起的血管松弛。这进一步暗示了CaSR诱导的通路和异构体TRPV4-TRPC1通道在调节血管张力中的作用。
Stimulation of calcium-sensing receptors (CaSR) by increasing the external calcium concentration (Ca2 +]o) induces endothelium-dependent vasorelaxation through nitric oxide (NO) production and activation of intermediate Ca2 +-activated K+ currents (IKCa) channels in rabbit mesenteric arteries. The present study investigates the potential role of heteromeric TRPV4-TRPC1 channels in mediating these CaSR-induced vascular responses. Immunocytochemical and proximity ligation assays showed that TRPV4 and TRPC1 proteins were expressed and co-localised at the plasma membrane of freshly isolated endothelial cells (ECs). In wire myography studies, increasing [Ca2 +]o between 1 and 6 mM induced concentration-dependent relaxations of methoxamine (MO)-induced pre-contracted tone, which were inhibited by the TRPV4 antagonists RN1734 and HC067047, and the externally-acting TRPC1 blocking antibody T1E3. In addition, CaSR-evoked NO production in ECs measured using the fluorescent NO indicator DAF-FM was reduced by RN1734 and T1E3. In contrast, [Ca2 +]o-evoked perforated-patch IKCa currents in ECs were unaffected by RN1734 and T1E3. The TRPV4 agonist GSK1016790A (GSK) induced endothelium-dependent relaxation of MO-evoked pre-contracted tone and increased NO production, which were inhibited by the NO synthase inhibitor L-NAME, RN1734 and T1E3. GSK activated 6pS cation channel activity in cell-attached patches from ECs which was blocked by RN1734 and T1E3. These findings indicate that heteromeric TRPV4-TRPC1 channels mediate CaSR-induced vasorelaxation through NO production but not IKCa channel activation in rabbit mesenteric arteries. This further implicates CaSR-induced pathways and heteromeric TRPV4-TRPC1 channels in regulating vascular tone.
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影响因子：
1.7
作者：
Kochukov MY;Balasubramanian A;Noel RC;Marrelli SP
通讯作者：
Marrelli SP
DOI：
10.1152/ajpheart.00717.2011
发表时间：
2012-02-01
影响因子：
4.8
作者：
Bubolz, Aaron H.;Mendoza, Suelhem A.;Zhang, David X.
通讯作者：
Zhang, David X.
影响因子：
8.3
作者：
Bukoski, RD;Bian, K;Mupanomunda, M
通讯作者：
Mupanomunda, M
DOI：
10.1111/j.1748-1716.2010.02217.x
发表时间：
2011-09
期刊：
Acta physiologica (Oxford, England)
影响因子：
--
作者：
Baylie RL;Brayden JE
通讯作者：
Brayden JE
影响因子：
20.1
作者：
Earley S;Gonzales AL;Crnich R
通讯作者：
Crnich R