Effects of aging on Ca2+ signaling in murine mesenteric arterial smooth muscle cells
Effects of aging on Ca2+ signaling in murine mesenteric arterial smooth muscle cells
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DOI：
10.1016/j.mad.2005.12.001
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发表时间：
2006-04-01
影响因子：
5.3
通讯作者：
Wilson, SM
中科院分区：
文献类型：
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作者：
del Corsso, C;Ostrovskaya, O;Wilson, SM
随着年龄增长，动脉平滑肌结构和功能会发生病理生理变化，并且有许多报道表明血管反应性随年龄增长而降低。虽然人们对动脉重塑以及随年龄增长的功能适应性了解较多，但对单个动脉肌细胞的生物物理适应性却知之甚少。胞质Ca2+信号传导，包括质膜上L型Ca2+通道的激活以及肌浆网上三磷酸肌醇（InsP(3)）受体和兰尼碱受体的激活，对血管张力和反应性至关重要。因此，我们验证了这样一个假设：从6个月和30个月大的C57B1/6小鼠分离出的肠系膜动脉平滑肌细胞中，衰老会导致L型通道功能表达降低以及兰尼碱受体和InsP(3)受体Ca2+信号传导的时间特性发生改变。使用透析全细胞电压钳技术并以Ba2+作为电荷载体对L型电流活动进行比较。使用Fura - 2荧光显微镜技术测量Ca2+信号传导。还使用电生理和免疫细胞化学方法研究细胞形态变化。老年小鼠的L型Ca2+电流幅度增加，但这与膜表面积增加约50%有关，这是由于细胞长度增加而非细胞宽度增加。因此，L型Ca2+电流密度随年龄增长保持不变，表明功能性通道表达未改变。相比之下，衰老与咖啡因刺激兰尼碱受体或苯肾上腺素激活InsP(3)受体所引起的Ca2+信号传导降低有关。这些随年龄增长而发生的变化可能与先前报道的肌源性反应性降低有关。（c）2006爱思唯尔爱尔兰有限公司。保留所有权利。
Pathophysiological changes in arterial smooth muscle structure and function occur with aging and there are a number of reports illustrating reductions in vascular responsiveness with aging. While much is known about arterial remodeling and functional adaptations with aging, very little is known about the biophysical adaptations in individual arterial myocytes. Cytosolic Ca2+ signaling, involving activation of L-type Ca2+ channels on the plasma membrane as well as InsP(3) and ryanodine receptors on the sarcoplasmic reticulum, is integral to vascular tone and reactivity. Thus, we tested the hypothesis that aging results in reductions in the functional expression of L-type channels and temporal aspects of ryanodine receptor and InsP(3) receptor Ca2+ signaling, in mesenteric arterial smooth muscle cells isolated from 6 and 30 months old C57B1/6 mice. Comparisons of L-type current activity were made using dialyzed, whole-cell voltage-clamp techniques and Ba2+ as charge carrier. Ca2+ signaling was measured using fura-2 fluorescence microscopy techniques. Cell morphological changes were also investigated using electrophysiological and immunocytochemical approaches. The amplitudes of L-type Ca2+ currents were increased in older mice, but this was associated with membrane surface area increases of similar to 50%, due to increases in cell length not cell width. Consequently, L-type Ca2+ current densities were preserved with age, indicating functional channel expression was unchanged. In contrast, aging was associated with decrements in Ca2+ signaling in response to either ryanodine receptor stimulation by caffeine or InsP(3) receptor activation with phenylephrine. These changes with aging may be related to the previously reported depression in myogenic reactivity. (c) 2006 Elsevier Ireland Ltd. All rights reserved.