Volume 12 Supplement 1
The effect of glutamate-gated chloride current on the excitability of a Purkinje cell: a modeling study
© Huang and De Schutter; licensee BioMed Central Ltd. 2011
Published: 18 July 2011
Purkinje neurons express, in high abundance, a glutamate gated chloride channel commonly known as the Excitatory Amino Acid Transporter subtype 4 (EAAT4). EAAT4 belongs to the family of glutamate transporters, which in mammalian nervous system is responsible for clearing synaptic glutamate . Studies of these transporters in heterogeneous expression systems demonstrated that in addition to glutamate transport, the binding of glutamate to the transporter activates a chloride current through the transporter with properties liken that of a channel and which is functionally independent from the transport process .
The role of the chloride channel in glutamate transporters is only known for the EAAT subtype 5 (EAAT5). On rod bipolar cell axon terminals, EAAT5 activation by glutamate results in membrane hyperpolarization, which consequently inhibits terminal glutamate release . Whether the chloride channel of EAAT4 has a physiological role in Purkinje neurons remains unknown. A synaptic model was developed to determine conditions in which the chloride channel of EAAT4 could influence Purkinje neuron function and whether these conditions are physiologically relevant.
The model comprises a single compartment with uniform distribution of AMPA receptors and EAAT4. The EAAT4 model is based on a 16-state kinetic model of EAAT2  using reaction rates of EAAT4 measured in . AMPA receptor conductance and absolute permeability of EAAT4 were parameterized for adjusting their respective current amplitudes. The model reproduced the EPSC and EAAT4 channel currents evoked in a Purkinje neuron by parallel fiber stimulation under conditions similar to those used in . The result serves as a basis for investigating the effects of the EAAT4 chloride current on Purkinje neuron excitability and intracellular chloride concentration.
- Tzingounis AV, Wadiche JI: Glutamate transporters: confining runaway excitation by shaping synaptic transmission. Nat Rev Neurosci. 2007, 8 (12): 935-947. 10.1038/nrn2274.View ArticlePubMedGoogle Scholar
- Vandenberg RJ, Huang S, Ryan RM: Slips, leaks and channels in glutamate transporters. Channels. 2008, 2 (1): 51-58. 10.4161/chan.2.1.6047.View ArticlePubMedGoogle Scholar
- Veruki ML, Morkve SH, Hartveit E: Activation of a presynaptic glutamate transporter regulates synaptic transmission through electrical signaling. Nat Neurosci. 2006, 9 (11): 1388-1396. 10.1038/nn1793.View ArticlePubMedGoogle Scholar
- Bergles DE, Tzingounis AV, Jahr CE: Comparison of coupled and uncoupled currents during glutamate uptake by GLT-1 transporters. J Neurosci. 2002, 22 (23): 10153-10162.PubMedGoogle Scholar
- Wadiche JI, Tzingounis AV, Jahr CE: Intrinsic kinetics determine the time course of neuronal synaptic transporter currents. Proc Natl Acad Sci. 2006, 103 (4): 1083-1087. 10.1073/pnas.0510476103.PubMed CentralView ArticlePubMedGoogle Scholar
This article is published under license to BioMed Central Ltd. This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.