Xia Y, Haddad G G
Department of Pediatrics (Section of Respiratory Medicine), Yale University School of Medicine, New Haven, Connecticut 06520.
J Comp Neurol. 1994 Jul 8;345(2):279-87. doi: 10.1002/cne.903450209.
Previous studies have shown that mammalian neuronal excitability increases with age, and this excitability may be related to development of Na+ channels. In addition, evidence suggests that Na+ channels are involved in the neuronal response to O2 deprivation. Because of this, we wished to examine the pharmacologic properties and neuroanatomical distribution of the Na+ channels in newborn brain and as a function of age. In this study, we used ligand-binding techniques and autoradiography with 3H-saxitoxin (STX) to investigate Na(+)-channel distribution in brains of rats at postnatal days 0, 3, 10, 21, 35, and 120. We found that (1) in each area examined, the Scatchard plots for STX binding were linear in both immature and mature brains in a ligand concentration range of 0.4-64 nM; the slopes, however, were different between areas or ages, with Kd values ranging between 1 and 5 nM; (2) STX-binding density was more than tenfold lower in the rostral brain and cerebellum at birth than in the adult and increased with age; (3) binding density in the newborn brainstem was higher than in other areas such as the cortex and cerebellum, which is opposite to the distribution in the adult; and (d) the brainstem had a different developing pattern with an early-peak density level (P10-21) and a lower adult level.(ABSTRACT TRUNCATED AT 250 WORDS)
以往的研究表明,哺乳动物神经元的兴奋性随年龄增长而增加,这种兴奋性可能与钠离子通道的发育有关。此外,有证据表明钠离子通道参与神经元对缺氧的反应。因此,我们希望研究新生大脑中钠离子通道的药理学特性和神经解剖分布及其随年龄的变化。在本研究中,我们使用配体结合技术和用³H-石房蛤毒素(STX)进行放射自显影,来研究出生后第0、3、10、21、35和120天大鼠大脑中钠离子通道的分布。我们发现:(1)在每个检测区域,在0.4 - 64 nM的配体浓度范围内,未成熟和成熟大脑中STX结合的Scatchard图均为线性;然而,不同区域或年龄之间的斜率不同,解离常数(Kd)值在1至5 nM之间;(2)出生时,延髓和小脑的STX结合密度比成年时低十多倍,且随年龄增加;(3)新生脑干中的结合密度高于皮质和小脑等其他区域,这与成年时的分布相反;(4)脑干具有不同的发育模式,密度水平在早期达到峰值(出生后10 - 21天),成年时水平较低。(摘要截选至250字)