Dreyfus C F, Friedman W J, Markey K A, Black I B
Brain Res. 1986 Aug 6;379(2):216-22. doi: 10.1016/0006-8993(86)90774-2.
The influence of membrane depolarization on the development and regulation of brain noradrenergic neurons was studied in explant cultures of the mouse locus coeruleus (l.c.). Exposure to the depolarizing agents veratridine or elevated K+ significantly increased the catalytic activity of tyrosine hydroxylase (TH), the rate-limiting enzyme in catecholamine biosynthesis. The effects of veratridine were prevented by tetrodotoxin, suggesting that transmembrane Na+ influx was necessary for the rise in TH. Morphometric analysis indicated that the rise in TH activity was not accompanied by altered TH-positive cell number or cell diameter. Rather, TH fluorescence intensity increased in each neuron, suggesting that depolarization increased TH per neuron. Immunoblot and densitometric analysis indicated that depolarization did, indeed, increase TH immunoreactive protein. Moreover, depolarization elevated enzyme activity in cultured neurons expressing the normal developmental increase in TH, as well as those in which plateau levels had already been attained. We conclude that depolarization and/or Na+ influx regulates a critical transmitter macromolecule in brain neurons, as in the periphery, by altering enzyme molecule number.
在小鼠蓝斑（l.c.）的外植体培养物中研究了膜去极化对脑去甲肾上腺素能神经元发育和调节的影响。暴露于去极化剂藜芦碱或高钾显著增加了酪氨酸羟化酶（TH）的催化活性，TH是儿茶酚胺生物合成中的限速酶。藜芦碱的作用可被河豚毒素阻止，这表明跨膜Na+内流是TH升高所必需的。形态计量学分析表明，TH活性的升高并未伴随着TH阳性细胞数量或细胞直径的改变。相反，每个神经元中的TH荧光强度增加，表明去极化增加了每个神经元中的TH。免疫印迹和光密度分析表明，去极化确实增加了TH免疫反应蛋白。此外，去极化提高了表达正常发育性TH增加的培养神经元以及那些已经达到平台水平的神经元中的酶活性。我们得出结论，去极化和/或Na+内流通过改变酶分子数量来调节脑神经元中一种关键的递质大分子，这与外周情况相同。
