Yu X M, Salter M W
Programme in Brain and Behaviour, Hospital for Sick Children, Toronto, Ontario, Canada.
Nature. 1998 Dec 3;396(6710):469-74. doi: 10.1038/24877.
The influx of Na+ is fundamental to electrical signalling in the nervous system and is essential for such basic signals as action potentials and excitatory postsynaptic potentials. During periods of bursting or high levels of discharge activity, large increases in intracellular Na+ concentration ([Na+]i) are produced in neuronal soma and dendrites. However, the intracellular signalling function of raised postsynaptic [Na+]i is unknown. Here we show that [Na+]i regulates the function of NMDA (N-methyl-D-aspartate) receptors, a principal subtype of glutamate receptor. NMDA-receptor-mediated whole-cell currents and NMDA-receptor single-channel activity were increased by raising [Na+]i and channel activity decreased upon lowering [Na+]i; therefore, the activity of NMDA channels tracks changes in [Na+]i. We found that the sensitivity of the channel to Na+ was set by a Src kinase that is associated with the channel. Raising [Na+]i selectively increased synaptic responses mediated by NMDA receptors, but not by non-NMDA receptors. Thus, the change in postsynaptic [Na+]i that occurs during neuronal activity is a signal for controlling the gain of excitatory synaptic transmission. This mechanism may be important for NMDA-receptor-dependent plasticity and toxicity in the central nervous system.
钠离子内流是神经系统电信号传导的基础，对于诸如动作电位和兴奋性突触后电位等基本信号至关重要。在爆发性活动或高放电水平期间，神经元胞体和树突内的细胞内钠离子浓度（[Na⁺]i）会大幅增加。然而，突触后升高的[Na⁺]i的细胞内信号传导功能尚不清楚。在此我们表明，[Na⁺]i调节NMDA（N-甲基-D-天冬氨酸）受体的功能，NMDA受体是谷氨酸受体的一种主要亚型。通过升高[Na⁺]i可增加NMDA受体介导的全细胞电流和NMDA受体单通道活性，而降低[Na⁺]i时通道活性则降低；因此，NMDA通道的活性跟踪[Na⁺]i的变化。我们发现通道对钠离子的敏感性由与该通道相关的Src激酶设定。升高[Na⁺]i选择性地增加了由NMDA受体介导的突触反应，但非NMDA受体介导的突触反应则未增加。因此，神经元活动期间发生的突触后[Na⁺]i变化是控制兴奋性突触传递增益的信号。这种机制可能对中枢神经系统中依赖NMDA受体的可塑性和毒性很重要。
