Abstract
To study differences in nature between synaptic and extrasynaptic AMPA-receptor in the adult brain, we recorded stimulus-evoked EPSC and AMPA-induced current response from hippocampal pyramidal neuron of rat brain slice under whole-cell patch clamp. Application of either NBQX or GYKI52466, AMPA antagonists, suppressed the both EPSC and AMPA-induced current response. Current(I)-voltage(V) relationship of the EPSC and AMPA-response intersected the voltage axis at 0 mV showing linear I-V curve. The AMPA-induced response was markedly augmented as much as twice of the control in the presence of cyclothiazide (CTZ), an inhibitor of desensitization of AMPA-receptor, whereas either EPSC or spontaneously evoked miniature EPSC was not affected at all by the CTZ. Furthermore, neither the amplitude nor the time course of the consecutive EPSCs evoked by repetitive stimulation of Schafer collateral at 100 Hz was not affected significantly by the presence of CTZ, although cumulative current responses to repetitive application of AMPA, which exhibited occlusion, were greatly augmented by CTZ in similar fashion to the single application of AMPA. The amplitude of the EPSC decreased in the presence of dihydrokainic acid (DHK), an inhibitor of GLT-1 glutamate transporter, but addition of CTZ to the DHK did not augment the EPSC amplitude. All these results suggest that synaptic AMPA receptor may lack the nature of desensitization unlike the extrasynaptic AMPA-receptor. [J Physiol Sci. 2006;56 Suppl:S163]
