Role of TRPC1 and TRPC3 channels in contraction and relaxation of mouse thoracic aorta.

Role of TRPC1 and TRPC3 channels in contraction and relaxation of mouse thoracic aorta.
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DOI:
10.1159/000342461
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发表时间:
2013
影响因子:
1.7
通讯作者:
Marrelli SP
Marrelli SP
中科院分区:
医学4区
文献类型:
--
作者:
Kochukov MY;Balasubramanian A;Noel RC;Marrelli SP

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规范的瞬时受体电位(TRPC)通道调节膜电位和细胞内钙离子。我们研究了TRPC1和TRPC3通道在小鼠主动脉血管收缩和松弛中的作用。用苯肾上腺素(Phe)和卡巴胆碱(CCH)测定了野生型(WT)、TRPC1KO和TRPC3KO小鼠的血管收缩和舒缩功能。测定原代培养的主动脉内皮细胞(EC)内钙离子浓度和新鲜分离的平滑肌细胞(SMC)的全细胞钾电流。与WT和TRPC3 KO相比,TRPC1 KO主动脉对Phe的收缩作用增强,这是由于BKCa通道的作用减弱。BKCa m RNA(主动脉)和全细胞电流(SMC)均较WT降低。BKCa通道阻断剂可使WT主动脉收缩增加至TRPC1KO水平。TRPC1KO和TRPC3KO的主动脉对CCH的舒张性降低,并伴随着ECCa+反应的降低。PYR3(TRPC3阻断剂)可降低WT小鼠EC对CCH的钙反应,但对TRPC3KO小鼠无明显影响。综上所述,TRPC1通过激活和/或表达SMC BKCa通道来减弱受体介导的收缩,而TRPC3不参与受体介导的收缩。TRPC1和TRPC3均参与主动脉内皮细胞内钙内流和血管松弛。
Canonical transient receptor potential (TRPC) channels modulate membrane potential and intracellular Ca2+. We examined the role of TRPC1 and TRPC3 channels in vasocontraction and relaxation in mouse aorta. Vasocontraction and relaxation of aorta from wild type (WT), TRPC1 KO, and TRPC3 KO mice were measured for phenylephrine (Phe) and carbachol (CCh). Intracellular Ca2+ was measured in primary aorta endothelial cells (EC) and whole cell K+ current in freshly isolated smooth muscle cells (SMC). TRPC1 KO aorta showed increased vasocontraction to Phe compared to WT and TRPC3 KO due to diminished role of BKCa channels. BKCa mRNA (aorta) and whole cell current (SMC) was reduced versus WT. Contraction in WT aorta was increased to TRPC1 KO level by BKCa channel inhibition. Relaxation to CCh was reduced in TRPC1 KO and TRPC3 KO aortas with concomitant reduction in EC Ca2+ response. Pyr3 (TRPC3 blocker) reduced the Ca2+ response to CCh in EC from WT, but not TRPC3 KO mice. In summary, TRPC1 attenuates receptor-mediated contraction through activation and/or expression of SMC BKCa channels while TRPC3 does not contribute to receptor-mediated constriction. Both TRPC1 and TRPC3 participate in EC Ca2+ influx and vasorelaxation of aorta.
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