title: Association of potassium channel Kv3.4 subunits with pre- and post-synaptic structures in brainstem and spinal cord.
abstract: Voltage-gated K+ channels (Kv) are divided into eight subfamilies (Kv1-8) and play a major role in determining the excitability of neurones. Members of the Kv3 subfamily are highly abundant in the CNS, with each Kv3 gene (Kv3.1-Kv3.4) exhibiting a unique pattern of expression, although single neurones can express more than one subtype. Of the Kv3 subunits relatively little is known of the Kv3.4 subunit distribution in the nervous system, particularly in the brainstem and spinal cord of the rat. We performed immunohistochemistry to determine both the cellular and sub-cellular distribution of the Kv3.4 subunit in these areas. Kv3.4 subunit immunoreactivity (Kv3.4-IR) was widespread, with dense, punctate staining in many regions including the intermediolateral cell column (IML) and the dorsal vagal nucleus (DVN), nucleus ambiguus (NA) and nucleus tractus solitarius (NTS). In the ventral horn a presynaptic location was confirmed by co-localization of Kv3.4-IR with the synaptic vesicle protein, SV2 and also with the glutamate vesicle markers vesicular glutamate transporter (VGluT) 1, VGluT2 or the glycine transporter GlyT2, suggesting a role for the channel in both excitatory and inhibitory neurotransmission. Electron microscopy confirmed a presynaptic terminal location of Kv3.4-IR in the VH, IML, DVN, NA and NTS. Interestingly however, patches of Kv3.4-IR were also revealed postsynaptically in dendritic and somatic structures throughout these areas. This staining was striking due to its localization at synaptic junctions at terminals with morphological features consistent with excitatory functions, suggesting an association with the postsynaptic density. Therefore the pre and postsynaptic localization of Kv3.4-IR suggests a role both in the control of transmitter release and in regulating neuronal excitability.
authors.affiliation: School of Biomedical Sciences, University of Leeds, Leeds LS2 9NQ, UK.
authors.forename: R E
authors.initials: RE
authors.lastname: Brooke
authors.forename: L
authors.initials: L
authors.lastname: Atkinson
authors.forename: T F C
authors.initials: TF
authors.lastname: Batten
authors.forename: S A
authors.initials: SA
authors.lastname: Deuchars
authors.forename: J
authors.initials: J
authors.lastname: Deuchars
mesh_terms: D026921:Amino Acid Transport Systems, Neutral / Q000378:metabolism; D000818:Animals; D001933:Brain Stem / Q000378:metabolism* / Q000648:ultrastructure; D002352:Carrier Proteins / Q000378:metabolism; D003712:Dendrites / Q000378:metabolism* / Q000648:ultrastructure; D050487:Glycine Plasma Membrane Transport Proteins; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D008562:Membrane Glycoproteins / Q000378:metabolism; D026901:Membrane Transport Proteins; D016253:Microscopy, Immunoelectron / Q000379:methods; D009419:Nerve Tissue Proteins / Q000378:metabolism; D015221:Potassium Channels / Q000378:metabolism*; D024642:Potassium Channels, Voltage-Gated; D017729:Presynaptic Terminals / Q000378:metabolism* / Q000648:ultrastructure; D051381:Rats; D017208:Rats, Wistar; D051670:Shaw Potassium Channels; D013116:Spinal Cord / Q000378:metabolism* / Q000648:ultrastructure; D013569:Synapses / Q000378:metabolism / Q000648:ultrastructure; D050598:Vesicular Glutamate Transport Protein 1; D050599:Vesicular Glutamate Transport Protein 2; D033921:Vesicular Transport Proteins
chemical_list: D026921:Amino Acid Transport Systems, Neutral; D002352:Carrier Proteins; D050487:Glycine Plasma Membrane Transport Proteins; C492015:KCNC4 protein, human; C492014:Kcnc4 protein, rat; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; D015221:Potassium Channels; D024642:Potassium Channels, Voltage-Gated; C493476:SLC17A6 protein, human; C493464:SLC17A7 protein, human; C493271:SLC6A5 protein, human; D051670:Shaw Potassium Channels; C493475:Slc17a6 protein, rat; C493466:Slc17a7 protein, rat; C493269:Slc6a5 protein, rat; C489614:Sv2a protein, mouse; C489618:Sv2a protein, rat; D050598:Vesicular Glutamate Transport Protein 1; D050599:Vesicular Glutamate Transport Protein 2; D033921:Vesicular Transport Proteins; C076414:SV2A protein, human