KINETICS AND MG2+ BLOCK OF N-METHYL-D-ASPARTATE RECEPTOR CHANNELS DURING POSTNATAL-DEVELOPMENT OF HIPPOCAMPAL CA3 PYRAMIDAL NEURONS

KINETICS AND MG2+ BLOCK OF N-METHYL-D-ASPARTATE RECEPTOR CHANNELS DURING POSTNATAL-DEVELOPMENT OF HIPPOCAMPAL CA3 PYRAMIDAL NEURONS
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DOI:
10.1016/0306-4522(95)00337-i
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发表时间:
1995-12-01
期刊:
影响因子:
3.3
通讯作者:
BREGESTOVSKI, P
BREGESTOVSKI, P
中科院分区:
医学3区
文献类型:
--
作者:
KHAZIPOV, R;RAGOZZINO, D;BREGESTOVSKI, P

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在未成年(出生后3-8天)和成年(出生后25-60天)大鼠海马脑片的CA 3锥体神经元中研究了N-甲基-D-天冬氨酸激活通道的电压依赖性镁阻滞和兴奋性突触电流的N-甲基-D-天冬氨酸成分。在所有的神经元研究的动力学的单通道开口在细胞贴附和由内而外的配置强烈调制细胞外Mg 2+,在电压依赖性的方式。未观察到N-甲基-D-天冬氨酸通道的Mg 2+敏感性的年龄依赖性差异。在生理浓度的外部Mg 2+(1.3 mM),N-甲基-D-天冬氨酸成分的兴奋性突触电流测量未成年和成年大鼠表现出类似的电压依赖性。在未成熟的神经元(出生后3-6天),N-甲基-D-天冬氨酸成分的兴奋性突触后电流衰减时程是一个单指数,平均时间常数约为300 ms。在老年动物的神经元的衰减是由一个双指数函数描述的快速组件(tau(f),54-130 ms)和一个缓慢的组件(tau(s),275-400 ms)。随着年龄的增长,快速组件的贡献增加和N-甲基-D-天冬氨酸成分的兴奋性突触后电流的衰减时程加速。结果表明,Mg ~(2+)对CA_3区锥体神经元N-甲基-D-天冬氨酸通道的阻滞作用不随发育而改变,但N-甲基-D-天冬氨酸受体通道的动力学特性受发育调控。
Voltage-dependent magnesium block of N-methyl-D-aspartate-activated channels, and the N-methyl-D-aspartate component of excitatory synaptic currents were studied in CA3 pyramidal neurons of hippocampal slices from immature (postnatal day 3-8) and adult (postnatal day 25-60) rats. In all neurons studied the kinetics of single-channel openings in cell-attached and inside-out configurations was strongly modulated by extracellular Mg2+, in a voltage-dependent manner. No age-dependent difference in the Mg2+ sensitivity of N-methyl-D-aspartate channels was observed. At physiological concentrations of external Mg2+ (1.3 mM), N-methyl-D-aspartate components of excitatory synaptic currents measured from immature and adult rats displayed a similar voltage-dependence. In immature neurons (postnatal day 3-6), the N-methyl-D-aspartate component of excitatory postsynaptic currents decay time-course was a single-exponential with an average time-constant of about 300 ms. In neurons from older animals the decay was described by a double-exponential function with both a fast component (tau(f), 54-130 ms) and a slow component (tau(s), 275-400 ms). With age, the contribution of the fast component increased and the decay time-course of the N-methyl-D-aspartate component of excitatory postsynaptic currents accelerated. It is concluded that the Mg2+ block of N-methyl-D-aspartate channels in CA3 pyramidal neurons does not change with development, but the kinetic properties of N-methyl-D-aspartate receptor channels are developmentally regulated.