Duckles S P, Tsai H, Buchholz J N
Department of Pharmacology, School of Medicine, University of California, Irvine, USA.
Life Sci. 1996;58(22):2029-35. doi: 10.1016/0024-3205(96)00194-4.
Age-related alterations in neuronal intracellular calcium regulation and neurotransmitter release have been widely reported. We have investigated the impact of age on neurotransmitter release and intracellular calcium buffering in adrenergic nerve endings of the isolated rat tail artery and on intracellular calcium in acutely dissociated cells from the superior cervical ganglion. Advancing age, from 6 to 27 months, resulted in significantly increased stimulation-evoked norepinephrine release from the isolated rat tail artery, an effect which persisted when neuronal and extraneuronal uptake were blocked with cocaine and deoxycorticosterone and presynaptic alpha adrenergic receptors were blocked with idazoxan. Alterations in extracellular calcium had significant effects on stimulation-evoked norepinephrine release, but these were much more marked in old, compared to young, arteries. Blockade of mitochondrial calcium accumulation with dinitrophenol had no significant effect on stimulation-evoked norepinephrine release from 6-month-old arteries, but in 20-month-old arteries, treatment with dinitrophenol resulted in a substantial increase in stimulation-evoked norepinephrine release. However, when extracellular calcium was increased to 5 mM in 6 month-old-arteries, then addition of dinitrophenol resulted in an increase in stimulation-evoked norepinephrine release. Measurement of intracellular calcium in acutely dissociated superior cervical ganglion cells using fura-2 revealed substantial age-related differences. Peak calcium transients in 20-month-old ganglion cells depolarized with 68 mM K+ were substantially higher than in 6-month-old cells. Together these findings support the hypothesis that in adrenergic nerves advancing age results in a disruption of intracellular calcium buffering leading to higher levels of intracellular calcium and increased transmitter release.
与年龄相关的神经元细胞内钙调节和神经递质释放的改变已被广泛报道。我们研究了年龄对分离的大鼠尾动脉肾上腺素能神经末梢神经递质释放和细胞内钙缓冲的影响，以及对颈上神经节急性解离细胞内钙的影响。年龄从6个月增长到27个月，导致分离的大鼠尾动脉中刺激诱发的去甲肾上腺素释放显著增加，当用可卡因和脱氧皮质酮阻断神经元和非神经元摄取以及用咪唑克生阻断突触前α肾上腺素能受体时，这种效应仍然存在。细胞外钙的改变对刺激诱发的去甲肾上腺素释放有显著影响，但与年轻动脉相比，这些影响在老年动脉中更为明显。用二硝基苯酚阻断线粒体钙积累对6个月大的动脉中刺激诱发的去甲肾上腺素释放没有显著影响，但在20个月大的动脉中，用二硝基苯酚处理导致刺激诱发的去甲肾上腺素释放大幅增加。然而，当6个月大的动脉中细胞外钙增加到5 mM时，添加二硝基苯酚会导致刺激诱发的去甲肾上腺素释放增加。使用fura-钙2测量急性解离的颈上神经节细胞内钙发现了与年龄相关的显著差异。用68 mM K+去极化的20个月大的神经节细胞中的钙瞬变峰值明显高于6个月大的细胞。这些发现共同支持了这样一种假设，即在肾上腺素能神经中，年龄增长会导致细胞内钙缓冲破坏，从而导致细胞内钙水平升高和递质释放增加。
