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EAATs, localized both to neurons and glia, are responsible for glutamate uptake. EAATs 1�C3 are expressed in the central nervous system where EAAT3 is neuronal and EAATs 1 and 2 are glial (O��Shea, 2002; Beart and O��Shea, 2007). At the high concentration (100 ��M) used in our prior study, TBOA blocks all three isoforms. In order to determine which subtypes are active at this particular synapse, we applied the EAAT2-selective blocker WAY213613 (0.5 ��M), TBOA at a low dose (10 ��M) to preferentially block EAAT3 in addition to EAAT2, or TBOA at a high dose (100 Bcl-2 inhibitor ��M) to additionally block EAAT1. In most experiments, all three of these drugs were applied sequentially. Representative traces can be seen in Figure ?Figure3A3A depicting the EPSC after addition of each EAAT inhibitor, and the time-course of the enhancement of the slow EPSC caused by the different inhibitors is shown in Figure ?Figure3B.3B. WAY213613 had no significant effect on the charge transfer of the SC compared to baseline (n = 5, baseline: 94.8 �� 8%; WAY213613: 93.7 �� 12%; p > 0.5), while 10 ��M TBOA approximately doubled the total charge transfer (n = 6, 215 �� 35.8%, p MMP23B ��M TBOA profoundly enhanced the slow EPSC as seen in our prior study, leading to a large increase in the total charge transfer (n = 7, 100 ��M TBOA: 831 �� 173%) and a substantial slowing of the EPSC decay so that the EPSC persisted for several seconds after the final train pulse as seen in Figure ?Figure3C3C. Figure 3 Blockade of EAAT1 and EAAT3 recruits a spillover- mediated slow AMPAR tail. (A) Representative average traces are shown for baseline and subsequent application of each drug. (B) The change in average ratio of the late EPSC relative to the charge transfer Ibrutinib ... To quantitate these observations, the decay of the EPSC after the final pulse in the train was fit by 3 exponentials: ��1 was constrained to a time constant of 1 s to fit the SC recruited by TBOA. The relative contributions of each component to the EPSC were profoundly affected by uptake inhibition (Figure ?(Figure3D).3D). The SC of the EPSC associated with ��2 was significantly enhanced in both doses of TBOA relative to baseline and WAY213613 conditions (baseline: n = 7, 10 �� 2%; WAY213613: n = 5, 15 �� 3%; 10 ��M TBOA: n = 6, 58 �� 12%; 100 ��M TBOA: n = 7, 49 �� 9%, p