About this item:

15 Views | 1 Download

Author Notes:

Dr. David D. Mott, Department of Pharmacology, Physiology, and Neuroscience, School of Medicine, University of South Carolina, Columbia, SC 29208. E-mail: dmott@med.sc.edu

We thank S. Misra, N. Ciliax, S. Zhang, and R. Shaw for excellent technical assistance.

Subjects:

Research Funding:

This work was supported by the Epilepsy Foundation (D.M.); National Alliance for Research on Schizophrenia and Depression (D.M.); the University Research Council of Emory University (D.M.); National Institute of Neurological Disorders and Stroke (R.D.); and the South Carolina Research Foundation (D.M.).

Keywords:

  • Science & Technology
  • Life Sciences & Biomedicine
  • Neurosciences
  • Neurosciences & Neurology
  • zinc
  • kainate receptor
  • CA3
  • glutamate receptor
  • mossy fiber
  • hippocampus
  • pH
  • MOSSY-FIBER SYNAPSES
  • HIPPOCAMPAL CA3 NEURONS
  • GLUTAMATE-RECEPTOR
  • SYNAPTIC-TRANSMISSION
  • NMDA RECEPTORS
  • GRANULE CELLS
  • ION CHANNELS
  • PHARMACOLOGICAL CHARACTERIZATION
  • AMPA RECEPTORS
  • SUBUNIT

pH-Dependent inhibition of kainate receptors by zinc

Tools:

Journal Title:

Journal of Neuroscience Nursing

Volume:

Volume 28, Number 7

Publisher:

, Pages 1659-1671

Type of Work:

Article | Final Publisher PDF

Abstract:

Kainate receptors contribute to synaptic plasticity and rhythmic oscillatory firing of neurons in corticolimbic circuits including hippocampal area CA3. We use zinc chelators and mice deficient in zinc transporters to show that synaptically released zinc inhibits postsynaptic kainate receptors at mossy fiber synapses and limits frequency facilitation of kainate, but not AMPA EPSCs during theta-pattern stimulation. Exogenous zinc also inhibits the facilitatory modulation of mossy fiber axon excitability by kainate but does not suppress the depressive effect of kainate on CA3 axons. Recombinant kainate receptors are inhibited in a subunit-dependent manner by physiologically relevant concentrations of zinc, with receptors containing the KA1 subunit being sensitive to submicromolar concentrations of zinc. Zinc inhibition does not alter receptor desensitization nor apparent agonist affinity and is only weakly voltage dependent, which points to an allosteric mechanism. Zinc inhibition is reduced at acidic pH. Thus, in the presence of zinc, a fall in pH potentiates kainate receptors by relieving zinc inhibition. Acidification of the extracellular space, as occurs during repetitive activity, may therefore serve to unmask kainate receptor neurotransmission. We conclude that zinc modulation of kainate receptors serves an important role in shaping kainate neurotransmission in the CA3 region.

Copyright information:

Copyright © 2008 Society for Neuroscience.

Export to EndNote