title: Lack of vesicular zinc in mossy fibers does not affect synaptic excitability of CA3 pyramidal cells in zinc transporter 3 knockout mice.
abstract: Zinc is found throughout the CNS in synaptic vesicles of glutamatergic neurons and has been suggested to have a modulatory role in the brain because of its interaction with voltage- and ligand-gated ion channels. We took advantage of zinc transporter 3 knockout mice, which lack vesicular zinc, to study the possible physiological role of this heavy metal in hippocampal mossy fiber neurotransmission. We examined postsynaptic responses evoked by mossy fiber activation, recorded in CA3 pyramidal cells in hippocampal slices prepared from zinc transporter 3 knockout and wild-type mice. Field-potential response threshold and amplitude, input-output curves, and paired-pulse evoked responses were the same in slices from zinc transporter 3 knockout and wild-type mice. Furthermore, neither amplitude nor duration of pharmacologically isolated N-methyl-D-aspartate, non-N-methyl-D-aspartate, GABA(A), and GABA(B) receptor-mediated postsynaptic potentials differed between zinc transporter 3 knockout and wild-type mice. There was no difference in the magnitude of epileptiform discharges evoked by repetitive stimulation or kainic acid application. However, in slices from zinc transporter 3 knockout mice, there was greater attenuation of GABA(A)-mediated inhibitory postsynaptic potentials during tetanic stimulation compared with slices from wild-type animals. We conclude that lack of vesicular zinc in mossy fibers does not significantly affect the mossy fiber-associated synaptic excitability of CA3 pyramidal cells; however, zinc may modulate GABAergic synaptic transmission under conditions of intensive activation.
authors.affiliation: Department of Pharmacology, University of Washington, Box 357280, Seattle, WA 98195-7280, USA. vlopants@u.washington.edu
authors.forename: V
authors.initials: V
authors.lastname: Lopantsev
authors.forename: H J
authors.initials: HJ
authors.lastname: Wenzel
authors.forename: T B
authors.initials: TB
authors.lastname: Cole
authors.forename: R D
authors.initials: RD
authors.lastname: Palmiter
authors.forename: P A
authors.initials: PA
authors.lastname: Schwartzkroin
mesh_terms: D000818:Animals; D002352:Carrier Proteins / Q000235:genetics / Q000502:physiology; D004594:Electrophysiology; D019706:Excitatory Postsynaptic Potentials; D006624:Hippocampus / Q000187:drug effects / Q000502:physiology; D007608:Kainic Acid / Q000494:pharmacology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D019599:Mossy Fibers, Hippocampal / Q000502:physiology*; D009433:Neural Inhibition / Q000187:drug effects; D018408:Patch-Clamp Techniques; D017966:Pyramidal Cells / Q000502:physiology*; D011963:Receptors, GABA-A / Q000502:physiology; D018080:Receptors, GABA-B / Q000502:physiology; D017470:Receptors, Glutamate / Q000502:physiology*; D016194:Receptors, N-Methyl-D-Aspartate / Q000502:physiology; D009435:Synaptic Transmission / Q000187:drug effects; D013572:Synaptic Vesicles / Q000502:physiology*; D015032:Zinc / Q000502:physiology*
chemical_list: D002352:Carrier Proteins; D011963:Receptors, GABA-A; D018080:Receptors, GABA-B; D017470:Receptors, Glutamate; D016194:Receptors, N-Methyl-D-Aspartate; C017800:zinc-binding protein; D015032:Zinc; D007608:Kainic Acid