Intrinsic kinetics determine the time course of neuronal synaptic transporter currents

Jacques I. Wadiche, Anastassios V. Tzingounis, Craig Jahr

Research output: Contribution to journalArticle

22 Citations (Scopus)

Abstract

Efficient clearance of synaptically released glutamate from the extracellular space is an absolute requirement for maintaining information processing in the central nervous system. In the cerebellum, clearance of glutamate relies on uptake by Bergmann glial cells and Purkinje cells (PCs). Uptake by PCs can be monitored by recording the synaptic transport current (STC) mediated by the PC-specific transporter excitatory amino acid transporter 4 (EAAT4). The slow time course of the PC STC has been used to argue that glutamate clearance is protracted. We find, however, that the time course of the STC is not affected by altering the amount of glutamate released at individual synapses or by partial transporter blockade, manipulations that would be expected to change the duration of the extracellular glutamate transient. Ion substitution experiments and kinetic modeling of the PC transporter current suggest that physiological levels of intracellular Na+ and glutamate slow the cycling rate of transporters and thereby lengthen the time course of STCs. The model predicts that PC transporters bind glutamate quickly but that the actual cycling rate of EAAT4 in physiological conditions is slow; therefore, the STC reflects the intrinsic kinetics of the glutamate transporter, not the rate of glutamate clearance.

Original languageEnglish (US)
Pages (from-to)1083-1087
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Volume103
Issue number4
DOIs
StatePublished - Jan 24 2006

Fingerprint

Purkinje Cells
Glutamic Acid
Excitatory Amino Acid Transporter 4
Amino Acid Transport System X-AG
Extracellular Space
Automatic Data Processing
Neuroglia
Synapses
Cerebellum
Central Nervous System
Ions

Keywords

  • Cerebellum
  • Climbing fiber
  • Parallel fiber
  • Purkinje

ASJC Scopus subject areas

  • Genetics
  • General

Cite this

Intrinsic kinetics determine the time course of neuronal synaptic transporter currents. / Wadiche, Jacques I.; Tzingounis, Anastassios V.; Jahr, Craig.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 103, No. 4, 24.01.2006, p. 1083-1087.

Research output: Contribution to journalArticle

Wadiche, Jacques I. ; Tzingounis, Anastassios V. ; Jahr, Craig. / Intrinsic kinetics determine the time course of neuronal synaptic transporter currents. In: Proceedings of the National Academy of Sciences of the United States of America. 2006 ; Vol. 103, No. 4. pp. 1083-1087.
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