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목적 : Signal transmission from photoreceptors to bipolar cells is mediated by glutamatergic synapses, and glutamate released from photoreceptors is taken up by various types of glutamate transporters. We sought to study how glutamate transporters affect signal transmission between photoreceptors and ON-bipolar cells in living mice by characterizing the effects of exogenous glutamate and glutamate transporter (EAAT) inhibitors on the scotopic ERG b-wave.
방법 : Dark-adapted wide-type mice (anesthetized, 8-12 week of age) were injected intravitreally in one eye with 1µL solution containing: (1) glutamate, (2) L-2-amino-4-phosphonobutanoic acid (L-AP4), (3) dihydrokainic acid (DHKA), or (4) a mixture of DHKA and glutamate. The other eye is used as the control. Scotopic flash ERG a- and b-waves were recorded 5, 20, 35, 50min after the injection, and the entire injection and recording procedures were carried out under infrared illumination to preserve the dark-adapted status
결과 : Intravitreal injection of glutamate, L-AP4 and DHKA reduced the b-wave amplitude, and the thresholds of such actions are 10mM, 10µM & 20mM for the three compounds, respectively. The inhibitory actions of glutamate and L-AP4 saturated at about 3.3M and 10mM respectively, and they reached maximum values 5 min after injection and gradually diminished over a period of 1hr. Co-injection of glutamate and a sub-threshold dose of DHKA increased the efficacy of glutamate and shifted the glutamate dose-response curve by about 1.5 log units to the left.
결론 : Our observation that DHKA increases glutamate efficacy indicates that part of the glutamate diffusion barrier is mediated by the DHKA-sensitive glutamate transporters in the Muller cells. The effects of other glutamate transporter inhibitors on glutamate actions are under investigation.
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