A DIRECT COMPARISON OF THE SINGLE-CHANNEL PROPERTIES OF SYNAPTIC AND EXTRASYNAPTIC NMDA RECEPTORS

The assumption that synaptic and extrasynaptic glutamate receptors are similar underpins many studies that have sought to relate the behavio r of channels in excised patches to the macroscopic properties of the EPSC. We have examined this issue for NMDA receptors in cerebellar gra nule cells, the small size of which allows the opening of individual s ynaptic NMDA channels to be resolved directly. We have used whole-cell patch-clamp recordings to determine the conductance and open time of NMDA channels activated during the EPSC and used cell-attached and out side-out recordings to examine NMDA receptors in somatic membrane. Con ductance and open time of synaptic channels were indistinguishable fro m those of extrasynaptic channels in cell-attached patches. However, t he channel conductance in outside-out patches was 20% lower than in ce ll-attached recordings. This change was partially reduced by dantrolen e and phalloidin, suggesting that it may involve depolymerization of a ctin following Ca2+ release from intracellular stores. Our results dem onstrate that synaptic and extrasynaptic NMDA receptors have similar m icroscopic properties. However, NMDA channel conductance is reduced fo llowing the formation of an outside-out patch.