Kafitz K W, Rose C R, Thoenen H, Konnerth A
Institut für Physiologic, Technische Universität München, Germany.
Nature. 1999 Oct 28;401(6756):918-21. doi: 10.1038/44847.
Neurotrophins are a family of structurally related proteins that regulate the survival, differentiation and maintenance of function of different populations of peripheral and central neurons. They are also essential for modulating activity-dependent neuronal plasticity. Here we show that neurotrophins elicit action potentials in central neurons. Even at low concentrations, brain-derived neurotrophic factor (BDNF) excited neurons in the hippocampus, cortex and cerebellum. We found that BDNF and neurotrophin-4/5 depolarized neurons just as rapidly as the neurotransmitter glutamate, even at a more than thousand-fold lower concentration. Neurotrophin-3 produced much smaller responses, and nerve growth factor was ineffective. The neurotrophin-induced depolarization resulted from the activation of a sodium ion conductance which was reversibly blocked by K-252a, a protein kinase blocker which prefers tyrosine kinase Trk receptors. Our results demonstrate a very rapid excitatory action of neurotrophins, placing them among the most potent endogenous neuro-excitants in the mammalian central nervous system described so far.
神经营养因子是一类结构相关的蛋白质家族，可调节外周和中枢不同神经元群体的存活、分化及功能维持。它们对于调节依赖活动的神经元可塑性也至关重要。在此我们表明，神经营养因子可在中枢神经元中引发动作电位。即使在低浓度下，脑源性神经营养因子（BDNF）也能兴奋海马体、皮层和小脑中的神经元。我们发现，BDNF和神经营养因子-4/5使神经元去极化的速度与神经递质谷氨酸一样快，即使浓度比谷氨酸低一千多倍。神经营养因子-3产生的反应要小得多，而神经生长因子则无效。神经营养因子诱导的去极化是由钠离子电导的激活所致，该电导被K-252a可逆性阻断，K-252a是一种偏好酪氨酸激酶Trk受体的蛋白激酶阻断剂。我们的结果证明了神经营养因子具有非常快速的兴奋作用，使其成为迄今为止所描述的哺乳动物中枢神经系统中最有效的内源性神经兴奋剂之一。
