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The Journal of Neuroscience, August 15, 2001, 21(16):5973-5983
Experimental Localization of Kv1 Family Voltage-Gated
K+ Channel  and  Subunits in Rat Hippocampal
Formation
Michael M.
Monaghan1,
James S.
Trimmer2, and
Kenneth J.
Rhodes1
1 Neuroscience, Wyeth-Ayerst Research, Princeton, New
Jersey 08543, and 2 Department of Biochemistry and Cell
Biology and Institute for Cell and Developmental Biology, State
University of New York, Stony Brook, New York 11794
In the mammalian hippocampal formation,
dendrotoxin-sensitive voltage-gated K+ (Kv) channels
modulate action potential propagation and neurotransmitter release.
To explore the neuroanatomical basis for this modulation, we used in situ hybridization, coimmunoprecipitation,
and immunohistochemistry to determine the subcellular localization of
the Kv channel subunits Kv1.1, Kv1.2, Kv1.4, and Kv 2 within the
adult rat hippocampus. Although mRNAs encoding all four of these Kv
channel subunits are expressed in the cells of origin of each major
hippocampal afferent and intrinsic pathway, immunohistochemical
staining suggests that the encoded subunits are associated with the
axons and terminal fields of these cells. Using an excitotoxin lesion
strategy, we explored the subcellular localization of these subunits in
detail. We found that ibotenic acid lesions of the entorhinal cortex
eliminated Kv1.1 and Kv1.4 immunoreactivity and dramatically reduced
Kv1.2 and Kv2 immunoreactivity in the middle third of the dentate
molecular layer, indicating that these subunits are located on axons
and terminals of entorhinal afferents. Similarly, ibotenic acid lesions of the dentate gyrus eliminated Kv1.1 and Kv1.4 immunoreactivity in the
stratum lucidum of CA3, indicating that these subunits are located on
mossy fiber axons. Kainic acid lesions of CA3 dramatically reduced
Kv1.1 immunoreactivity in the stratum radiatum of CA1-CA3, indicating
that Kv1.1 immunoreactivity in these subfields is associated with the
axons and terminals of the Schaffer collaterals. Together with the
results of coimmunoprecipitation analyses, these data suggest that
action potential propagation and glutamate release at excitatory
hippocampal synapses are directly modulated by Kv1 channel complexes
predominantly localized on axons and nerve terminals.
Key words:
long-term potentiation; synaptic plasticity; A-current; dendrotoxin; ibotenic acid; perforant path; mossy fiber; Schaffer
collateral; Shaker
Copyright © 2001 Society for Neuroscience 0270-6474/01/21165973-11$05.00/0
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