许多甘氨酸突触中γ-氨基丁酸与甘氨酸共存。在2008年2月28日的《神经元》(Neuron)封面文章中,Lu等人证明了γ-氨基丁酸直接调节甘氨酸受体对甘氨酸的应答响应,从而产生适宜听觉功能的快速抑制作用。囊泡中同时包含强弱激动剂是进行突触后微调的作用机制。
神经元放电模式是通过集中神经兴奋与抑制形成,在程度和持续时间上都非常精确。在听觉脑干核里,甘氨酸抑制剂以其快速衰减动力学而著称,但作用机制一直不为人所知。
在最新研究中,科学家通过甘氨酸与天然或重组的甘氨酸受体相互作用,发现该作用的衰减时间是通过γ-氨基丁酸增加而增加的,其中γ-氨基丁酸是甘氨酸受体的弱局部激动剂。激动剂接触期间的系统变异显示,快速突触时段可能是在亚毫秒级尺度上,在生理浓度下与甘氨酸和γ-氨基丁酸的混合物接触而达成。相应地,突触前的终端一般包含两个发送器,通过耗尽γ-氨基丁酸的终端来减缓甘氨酸突触电流。
因此,与甘氨酸共释放的γ-氨基丁酸,通过直接作用于甘氨酸受体与缩短有效抑制的时间的方式来加速甘氨酸的传递。研究人员猜测,也许将强弱激动剂包裹在囊泡中是一个普遍的方法,通过这种方式突触前神经元可以调节突触后的反应持续时间。(科学网 武彦文/编译)
生物谷推荐原始出处:
(Neuron),Vol 57, 524-535, 28 February 2008,Tao Lu, Laurence O. Trussell
Glycinergic Transmission Shaped by the Corelease of GABA in a Mammalian Auditory Synapse
Tao Lu, Maria E. Rubio, and Laurence . Trussell
Summary
The firing pattern of neurons is shaped by the convergence of excitation and inhibition, each with finely tuned magnitude and duration. In an auditory brainstem nucleus, glycinergic inhibition features fast decay kinetics, the mechanism of which is unknown. By applying glycine to native or recombinant glycine receptors, we show that response decay times are accelerated by addition of GABA, a weak partial agonist of glycine receptors. Systematic variation in agonist exposure time revealed that fast synaptic time course may be achieved with submillisecond exposures to mixtures of glycine and GABA at physiological concentrations. Accordingly, presynaptic terminals generally contained both transmitters, and depleting terminals of GABA slowed glycinergic synaptic currents. Thus, coreleased GABA accelerates glycinergic transmission by acting directly on glycine receptors, narrowing the time window for effective inhibition. Packaging both weak and strong agonists in vesicles may be a general means by which presynaptic neurons regulate the duration of postsynaptic responses.