Maturation and long-term hypoxia alters Ca2+-induced Ca2+ release in sheep cerebrovascular sympathetic neurons.
Maturation and long-term hypoxia alters Ca2+-induced Ca2+ release in sheep cerebrovascular sympathetic neurons.
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DOI：
10.1152/japplphysiol.00363.2009
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发表时间：
2009-10
影响因子：
3.3
通讯作者：
Erik J Behringer;L. Leite;Nickolaus E. Buchholz;Michael Keeney;W. Pearce;C. Vanterpool;S. Wilson;J. Buchholz
中科院分区：
文献类型：
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作者：
Erik J Behringer;L. Leite;Nickolaus E. Buchholz;Michael Keeney;W. Pearce;C. Vanterpool;S. Wilson;J. Buchholz
来自颈上神经节（SCG）的交感神经对脑血管的生长和功能的贡献与整个成熟过程以及对高原长期缺氧（LTH）造成的心血管应激的反应有关。SCG交感神经元的功能依赖于细胞内Ca2+浓度（[Ca2+]i）信号，这一信号受到光滑内质网（SER）中Ca（2+）诱导的Ca2+释放（CICR）过程的强烈影响。在这项研究中，我们使用绵羊SCG神经元模型来验证成熟降低胎儿SCG神经元的CICR和高海拔LTH降低CICR的假设，而在成人SCG神经元中则没有。我们发现，在常氧胎儿的SCG细胞中，CICR对电场刺激（EFS）诱发的[Ca2+]i瞬变的贡献最大，并被LTH消除。CICR的下降与LTH期间胎儿SCG细胞sarco（内）质网Ca(2+)- atp酶（SERCA）功能的降低有关，将SER Ca2+水平降低到Ca2+内流和CICR耦合所需的阈值以下。从胎儿到成人，CICR的降低可能反映了ryanodine受体亚型2和3水平的降低以及SERCA功能的降低。与胎儿相比，成年SCG细胞的CICR功能在LTH的作用下得以维持，这可能反映了调节CICR过程的其他机制的改变。由于CICR在脑血管内交感神经元的功能中起着重要作用，从胎儿对血管损伤的易感性来看，胎儿失去这种信号机制可能会对LTH的适应产生影响。
The contribution of sympathetic nerves arising from the superior cervical ganglia (SCG) toward the growth and function of cerebral blood vessels is pertinent throughout maturation as well as in response to cardiovascular stress imposed by high-altitude long-term hypoxia (LTH). The function of SCG sympathetic neurons is dependent on intracellular Ca2+ concentration ([Ca2+]i) signaling, which is strongly influenced by a process known as Ca(2+)-induced Ca2+ release (CICR) from the smooth endoplasmic reticulum (SER). In this study, we used the sheep SCG neuronal model to test the hypotheses that maturation decreases CICR and high-altitude LTH depresses CICR in fetal SCG neurons but not in those of the adult. We found that the contribution of CICR to electric field stimulation (EFS)-evoked [Ca2+]i transients was greatest in SCG cells from normoxic fetuses and was abolished by LTH. The decline in CICR was associated with a reduction in sarco(endo)plasmic reticulum Ca(2+)-ATPase (SERCA) function in fetal SCG cells during LTH, reducing SER Ca2+ levels below the threshold needed for the coupling of Ca2+ influx and CICR. With respect to the maturation from the fetus to adult, the decrease in CICR may reflect both a reduction in the levels of ryanodine receptor isoforms 2 and 3 and SERCA function. In response to LTH and in contrast to the fetus, CICR function in adult SCG cells is maintained and may reflect alterations in other mechanisms that modulate the CICR process. As CICR is instrumental in the function of sympathetic neurons within the cerebrovasculature, the loss of this signaling mechanism in the fetus may have consequences for the adaptation to LTH in terms of fetal susceptibility to vascular insults.