Soto David, Coombs Ian D, Kelly Leah, Farrant Mark, Cull-Candy Stuart G
Department of Pharmacology, University College London, Gower Street, London WC1E 6BT, UK.
Nat Neurosci. 2007 Oct;10(10):1260-7. doi: 10.1038/nn1966. Epub 2007 Sep 16.
Endogenous polyamines profoundly affect the activity of various ion channels, including that of calcium-permeable AMPA-type glutamate receptors (CP-AMPARs). Here we show that stargazin, a transmembrane AMPAR regulatory protein (TARP) known to influence transport, gating and desensitization of AMPARs, greatly reduces block of CP-AMPARs by intracellular polyamines. By decreasing CP-AMPAR affinity for cytoplasmic polyamines, stargazin enhances the charge transfer following single glutamate applications and eliminates the frequency-dependent facilitation seen with repeated applications. In cerebellar stellate cells, which express both synaptic CP-AMPARs and stargazin, we found that the rectification and unitary conductance of channels underlying excitatory postsynaptic currents were matched by those of recombinant AMPARs only when the latter were associated with stargazin. Taken together, our observations establish modulatory actions of stargazin that are specific to CP-AMPARs, and suggest that during synaptic transmission the activity of such receptors, and thus calcium influx, is fundamentally changed by TARPs.
内源性多胺对包括钙通透型AMPA受体（CP-AMPARs）在内的多种离子通道活性有深远影响。我们在此表明，stargazin作为一种已知可影响AMPA受体转运、门控和脱敏的跨膜AMPA受体调节蛋白（TARP），能极大地减少细胞内多胺对CP-AMPARs的阻断。通过降低CP-AMPARs对细胞质多胺的亲和力，stargazin增强了单次应用谷氨酸后的电荷转移，并消除了重复应用时出现的频率依赖性易化现象。在同时表达突触CP-AMPARs和stargazin的小脑星状细胞中，我们发现，仅当重组AMPA受体与stargazin结合时，兴奋性突触后电流所依赖通道的整流和单位电导才与重组AMPA受体的相匹配。综上所述，我们的观察结果确立了stargazin对CP-AMPARs具有特异性的调节作用，并表明在突触传递过程中，此类受体的活性以及由此导致的钙内流会因TARPs而发生根本性改变。
