Juhász Gábor, Vass Gabriella, Bozsó Zsolt, Budai Dénes, Penke Botond, Szegedi Viktor
Department of Medical Chemistry, University of Szeged, Szeged, Hungary.
Brain Res. 2008 Oct 3;1233:20-6. doi: 10.1016/j.brainres.2008.05.032. Epub 2008 May 21.
The large family of heterodimeric, transmembrane cell adhesion receptors, integrins mediate numerous functions in the immature and adult CNS. Integrins are described to modulate basic synaptic function and plasticity, and to modulate the activity of the two major excitatory ionotrophic receptor subclass, NMDA and AMPA receptors. We further addressed the role of integrin activation in the normal excitatory synaptic function by utilizing in vivo single-unit recordings combined with microiontophoretic drug application in the CA1 region of the rat. Cells were excited by alternating NMDA and AMPA ejection, while integrin activation was achieved by the ejection of an RGD sequence containing pentapeptide in low and high concentration. Low integrin activation resulted in increased NMDA and decreased AMPA induced firing rate, while high RGD concentration enhanced both types of elicited responses. The control pentapeptide, pentaglycine had no effect on NMDA or AMPA evoked firing rate in either low or high concentration. These results suggest a bidirectional, dose dependent action of integrin activation on basic synaptic transmission, which may underlie the long term synaptic plasticity changes modulated by integrins.
整合素是异二聚体跨膜细胞粘附受体大家族的成员，在未成熟和成熟的中枢神经系统中发挥多种功能。整合素被描述为可调节基本突触功能和可塑性，并调节两种主要的兴奋性离子型受体亚类——NMDA和AMPA受体的活性。我们通过在大鼠CA1区进行体内单单位记录并结合微量离子电泳药物应用，进一步探讨了整合素激活在正常兴奋性突触功能中的作用。通过交替喷射NMDA和AMPA来激发细胞，同时通过喷射低浓度和高浓度的含RGD序列的五肽来实现整合素激活。低整合素激活导致NMDA诱导的放电频率增加，而AMPA诱导的放电频率降低，而高浓度的RGD增强了两种类型的诱发反应。对照五肽甘氨酸五肽在低浓度或高浓度下对NMDA或AMPA诱发的放电频率均无影响。这些结果表明整合素激活对基本突触传递具有双向、剂量依赖性作用，这可能是整合素调节长期突触可塑性变化的基础。
