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The Journal of Neuroscience, March 14, 2007, 27(11):2943-2947; doi:10.1523/JNEUROSCI.0118-07.2007

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Brief Communications
The Glutamate-Activated Anion Conductance in Excitatory Amino Acid Transporters Is Gated Independently by the Individual Subunits

Hans Peter Koch, Ronald Lane Brown, and Hans Peter Larsson

Neurological Sciences Institute, Oregon Health & Science University, Beaverton, Oregon 97006

Correspondence should be addressed to Hans Peter Larsson, Neurological Sciences Institute, Oregon Health & Science University, Beaverton, OR 97006. Email: larssonp{at}ohsu.edu

Excitatory amino acid transporters (EAATs) use sodium and potassium gradients to remove glutamate from the synapse and surrounding extracellular space, thereby sustaining efficient synaptic transmission and maintaining extracellular glutamate concentrations at subneurotoxic levels. In addition to sodium-driven glutamate uptake, EAATs also mediate a glutamate-activated chloride conductance via a channel-like mechanism. EAATs are trimeric proteins and are thought to comprise three identical subunits. Previous studies have shown that the sodium-driven uptake of glutamate occurs independently in each of the three subunits. In contrast, a recent study reports high Hill coefficients for the activation of EAAT anion currents by glutamate and suggests that the subunits function cooperatively in gating the chloride conductance. In the present work, we find that the Hill coefficient for the activation of the anion current by glutamate is 1 in both EAAT3 and EAAT4. Furthermore, we also used fluorescent labeling and inactivation correlation on EAAT3 and EAAT4 to determine whether the glutamate-activated chloride conductance is gated independently or cooperatively by the transporters. We found that both glutamate uptake currents and glutamate-activated chloride currents are mediated independently by each subunit of an EAAT multimer. It has been suggested that EAAT subtypes with particularly large anion conductances can directly influence the excitability of presynaptic terminals in certain neurons. Thus, the finding that the anion conductance is gated independently, rather than cooperatively, is important because it significantly alters predictions of the influence that EAAT-mediated anion currents will have on synaptic transmission at low glutamate concentrations.

Key words: anion conductance; chloride; independence; cooperativity; FLIC; glutamate transporter

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Received Oct. 2, 2006; revised Feb. 12, 2007; accepted Feb. 15, 2007.

Correspondence should be addressed to Hans Peter Larsson, Neurological Sciences Institute, Oregon Health & Science University, Beaverton, OR 97006. Email: larssonp{at}ohsu.edu

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