Intravascular pressure regulates local and global Ca2+ signaling in cerebral artery smooth muscle cells
Intravascular pressure regulates local and global Ca2+ signaling in cerebral artery smooth muscle cells
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DOI：
10.1152/ajpcell.2001.281.2.c439
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发表时间：
2001-08-01
影响因子：
5.5
通讯作者：
Jaggar, JH
中科院分区：
文献类型：
--
作者：
Jaggar, JH
使用激光扫描共聚焦显微镜和荧光 Ca2+ 指示剂 Fluo 3，在大鼠脑动脉（类似于 150 mm）中研究了血管内压力对平滑肌细胞和动脉直径的细胞内 Ca2+ 信号的调节。压力从 10 mmHg 升高至 60 mmHg 使 Ca2+ 火花频率增加 2.6 倍，Ca2+ 波频率增加 1.9 倍，以及总体细胞内 Ca2+ 浓度([Ca2+](i)) 是平滑肌细胞和收缩动脉的 1.4 倍。 Ryanodine (10 muM) 是一种 ryanodine 敏感 Ca2+ 释放通道抑制剂，或 thapsigargin (100 nM) 是一种肌浆网 Ca2+-ATPase 抑制剂，可消除火花和波、升高整体 [Ca2+](i) 并收缩加压 (60 mmHg) 动脉。地尔硫卓 (25 muM) 是一种电压依赖性 Ca2+ 通道 (VDCC) 阻滞剂，可显着减少火花、波和整体 [Ca2+](i)，并扩张加压 (60 mmHg) 动脉。稳定的膜去极化提高了类似于压力的 Ca2+ 信号传导，并增加了瞬态 Ca2+ 敏感的 K+ 通道电流频率 e 倍，大约为 7 mV，而这些效应可被 VDCC 阻滞剂阻止。数据与压力引起稳定的膜去极化激活 VDCC 的假设一致，导致火花频率、波频率和整体 [Ca2+](i) 升高。此外，压力通过整体 [Ca2+](i) 的升高引起收缩，而火花和波对加压至 10 至 60 mmHg 的动脉中的整体 [Ca2+](i) 没有显着贡献，其净效应是对抗收缩。
The regulation of intracellular Ca2+ signals in smooth muscle cells and arterial diameter by intravascular pressure was investigated in rat cerebral arteries (similar to 150 mum) using a laser scanning confocal microscope and the fluorescent Ca2+ indicator fluo 3. Elevation of pressure from 10 to 60 mmHg increased Ca2+ spark frequency 2.6-fold, Ca2+ wave frequency 1.9-fold, and global intracellular Ca2+ concentration ([Ca2+](i)) 1.4-fold in smooth muscle cells, and constricted arteries. Ryanodine (10 muM), an inhibitor of ryanodine-sensitive Ca2+ release channels, or thapsigargin (100 nM), an inhibitor of the sarcoplasmic reticulum Ca2+-ATPase, abolished sparks and waves, elevated global [Ca2+](i), and constricted pressurized (60 mmHg) arteries. Diltiazem (25 muM), a voltage-dependent Ca2+ channel (VDCC) blocker, significantly reduced sparks, waves, and global [Ca2+](i), and dilated pressurized (60 mmHg) arteries. Steady membrane depolarization elevated Ca2+ signaling similar to pressure and increased transient Ca2+-sensitive K+ channel current frequency e-fold for similar to7 mV, and these effects were prevented by VDCC blockers. Data are consistent with the hypothesis that pressure induces a steady membrane depolarization that activates VDCCs, leading to an elevation of spark frequency, wave frequency, and global [Ca2+](i). In addition, pressure induces contraction via an elevation of global [Ca2+](i), whereas the net effect of sparks and waves, which do not significantly contribute to global [Ca2+](i) in arteries pressurized to between 10 and 60 mmHg, is to oppose contraction.