Early postnatal switch in magnesium sensitivity of NMDA receptors in rat CA1 pyramidal cells
Early postnatal switch in magnesium sensitivity of NMDA receptors in rat CA1 pyramidal cells
复制标题
DOI：
10.1111/j.1469-7793.1999.00099.x
复制
发表时间：
1999-11-15
影响因子：
5.5
通讯作者：
Yaari, Y
中科院分区：
文献类型：
--
作者：
Kirson, ED;Schirra, C;Yaari, Y
1. 采用全细胞膜片湿法记录1 ~ 40日龄大鼠海马CA1锥体细胞中离子电泳诱导的n -甲基-d -天冬氨酸（NMDA）受体介导电流（I-NMDA），以表征NMDA受体对Mg2+敏感性的发育变化。细胞外Mg2+阻断I-NMDA的剂量-反应关系表明，Mg2+与NMDA受体的高亲和力结合，膜电位大于-60 mV，与出生后年龄无关。去极化细胞通过降低NMDA受体对Mg2+的亲和力来解锁NMDA受体。在出生后第4天（P4），去极化解封NMDA受体的效果显著增加，使受体具有更大的电压依赖性。NR2B亚基特异性NMDA拮抗剂伊芬普罗地尔降低了所有年龄段锥体细胞中的I-NMDA。I-NMDA对伊芬普罗地尔的敏感性在出生后第一周最大，此后逐渐降低，表明NR2B亚基NMDA受体在出生后第一周对I-NMDA的贡献增强。在出生后第一周，不敏感的INMDA组分比总I-NMDA具有更低的电压依赖性。在老年锥体细胞中，对伊芬prodi不敏感组分和总I-NMDA的电压依赖性相似。在另一组CA1锥体细胞中，使用单细胞反转录和聚合酶链反应（RT-PCR）来表征NMDA亚基mRNA表达的伴随发育变化。50%的细胞在出生后第一周检测到NR2D亚基mRNA，随后消失。表达NR2A和NR2B亚基的细胞比例在出生后的前5周保持相对稳定。我们得出结论，海马CA1锥体细胞中的NMDA受体在所有年龄段都能被Mg2+有效阻断。4天后，它们在去极化膜电位下对Mg2+的敏感性大大降低。Mg2+与NMDA受体结合的电压控制的这种出生后开关可能是由于发育中的CA1锥体细胞中NR2D亚基表达下调。
1. Whole-cell patch-damp recordings of iontophoretically induced N-methyl-D-aspartate (NMDA) receptor-mediated currents (I-NMDA) in CA1 pyramidal cells in hippocampal slices from 1- to 40-day-old rats were used to characterize developmental changes in the Mg2+ sensitivity of NMDA receptors.2. The dose-response relations for extracellular Mg2+ blockade of I-NMDA indicated a high affinity binding of Mg2+ to NMDA receptors at membrane potentials more negative than -60 mV, independent of postnatal age.3. Depolarizing the cells unblocked NMDA receptors by decreasing their affinity for Mg2+. The efficacy of depolarization in unblocking NMDA receptors markedly increased after postnatal day 4 (P4), endowing the receptors with a greater voltage dependence.4. The NR2B subunit-specific NMDA antagonist ifenprodil reduced I-NMDA in pyramidal cells of all ages. The sensitivity of I-NMDA to ifenprodil was greatest during the first postnatal week and decreased thereafter, indicating an enhanced contribution of NR2B subunit-containing NMDA receptors to I-NMDA in the first week after birth.5. In the first postnatal week, the ifenprodil-insensitive INMDA component had a lower voltage dependence than the total I-NMDA. In older pyramidal cells, the voltage dependence of the ifenprodil-insensitive component and the total I-NMDA were similar.6. In another set of CA1 pyramidal cells, single-cell reverse transcription and polymerase chain reaction (RT-PCR) were used to characterize concomitant developmental changes in NMDA subunit mRNA expression. The mRNA for the NR2D subunit was detected during the first postnatal week in 50% of the cells and disappeared thereafter. The proportion of cells expressing the NR2A and NR2B subunits remained relatively constant throughout the first five postnatal weeks.7. We conclude that NMDA receptors in hippocampal CA1 pyramidal cells are effectively blocked by Mg2+ at all ages. After 4 days they become much less sensitive to Mg2+ at depolarized membrane potentials. This postnatal switch in voltage control of Mg2+ binding to NMDA receptors may be due to the downregulation of NR2D subunit expression in developing CA1 pyramidal cells.