Vascular tone and Ca(2+) signaling in murine cremaster muscle arterioles in vivo.

Vascular tone and Ca(2+) signaling in murine cremaster muscle arterioles in vivo.
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DOI:
10.1111/micc.12025
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发表时间:
2013-04
期刊:
Microcirculation (New York, N.Y. : 1994)
影响因子:
--
通讯作者:
Wier WG
Wier WG
中科院分区:
其他
文献类型:
--
作者:
Mauban JR;Zacharia J;Zhang J;Wier WG

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我们试图确定体内骨骼肌小动脉基础状态“张力”的一些分子要求,以及是否涉及异步Ca2+波。将麻醉后的exMLCK和smGCaMP2生物传感器小鼠的肌肌外化,用广角、共聚焦或多光子显微镜观察荧光小动脉,观察Ca2+信号和小动脉直径。小动脉基态张力约50%。局部阻断Ang-II受体(AT1)或α1-肾上腺素受体(α1-AR)对直径无影响,完全阻断交感神经活动(SNA)也无影响。磷脂酶C的抑制导致扩张接近Ca2+游离(被动)直径,暴露于硝苯地平或2-APB也是如此。用SKF96365治疗时,小动脉也得到扩张。平滑肌细胞中exMLCK荧光(比率)或GCaMP2荧光的高分辨率成像未能显示Ca2+波(尽管Ca2+波/瞬态很容易被小动脉中的生物传感器检测到,离体)。肌细动脉的血管张力约为50%,这与α1-AR、AT1R或SNA无关。需要PLC活性,l型Ca2+通道,2-APB-和skf96365敏感通道。传播Ca2+波不存在。除了产生Ca2+波外,PLC和InsP3R在体内血管张力中起着关键作用。
We sought to determine some of the molecular requirements for basal state “tone” of skeletal muscle arterioles in vivo, and whether asynchronous Ca2+ waves are involved or not. Cremaster muscles of anesthetized exMLCK and smGCaMP2 biosensor mice were exteriorized, and the fluorescent arterioles were visualized with wide-field, confocal or multiphoton microscopy to observe Ca2+ signaling and arteriolar diameter. Basal state tone of the arterioles was~50%. Local block of Ang-II receptors (AT1) or α1-adrenoceptors (α1-AR) had no effect on diameter, nor did complete block of sympathetic nerve activity (SNA). Inhibition of phospholipase C caused dilation nearly to the Ca2+-free (passive) diameter, as did exposure to nifedipine or 2-APB. Arterioles were also dilated when treated with SKF96365. High-resolution imaging of exMLCK fluorescence (ratio) or GCaMP2 fluorescence in smooth muscle cells failed to reveal Ca2+ waves (although Ca2+ waves/transients were readily detected by both biosensors in small arteries, ex vivo). Arterioles of cremaster muscle have vascular tone of ~50%, which is not due to α1-AR, AT1R, or SNA. PLC activity, L-type Ca2+ channels, 2-APB- and SKF96365-sensitive channels are required. Propagating Ca2+ waves are not present. A key role for PLC and InsP3R in vascular tone in vivo, other than producing Ca2+ waves, is suggested.
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