Altered expression and localization of hippocampal A-type potassium channel subunits in the pilocarpine-induced model of temporal lobe epilepsy.
Altered ion channel expression and/or function may contribute to the development of certain human epilepsies. In rats, systemic administration of pilocarpine induces a model of human temporal lobe epilepsy, wherein a brief period of status epilepticus (SE) triggers development of spontaneous recurrent seizures that appear after a latency of 2-3 weeks. Here we investigate changes in expression of A-type voltage-gated potassium (Kv) channels, which control neuronal excitability and regulate action potential propagation and neurotransmitter release, in the pilocarpine model of epilepsy. Using immunohistochemistry, we examined the expression of component subunits of somatodendritic (Kv4.2, Kv4.3, KChIPl and KChIP2) and axonal (Kv1.4) A-type Kv channels in hippocampi of pilocarpine-treated rats that entered SE. We found that Kv4.2, Kv4.3 and KChIP2 staining in the molecular layer of the dentate gyrus changes from being uniformly distributed across the molecular layer to concentrated in just the outer two-thirds. We also observed a loss of KChIP1 immunoreactive interneurons, and a reduction of Kv4.2 and KChIP2 staining in stratum radiatum of CA1. These changes begin to appear 1 week after pilocarpine treatment and persist or are enhanced at 4 and 12 weeks. As such, these changes in Kv channel distribution parallel the acquisition of recurrent spontaneous seizures as observed in this model. We also found temporal changes in Kv1.4 immunoreactivity matching those in Timm's stain, being expanded in stratum lucidum of CA3 and in the inner third of the dentate molecular layer. Among pilocarpine-treated rats, changes were only observed in those that entered SE. These changes in A-type Kv channel expression may contribute to hyperexcitability of dendrites in the associated hippocampal circuits as observed in previous studies of the effects of pilocarpine-induced SE.
Monaghan
M M
MM
Neuroscience, Wyeth Discovery Research, CN8000, Princeton, NJ 08543, USA.
Menegola
M
M
Vacher
H
H
Rhodes
K J
KJ
Trimmer
J S
JS
D000818:Animals; D004195:Disease Models, Animal; D000076122:Disks Large Homolog 4 Protein; D004833:Epilepsy, Temporal Lobe / Q000139:chemically induced* / Q000473:pathology*; D005786:Gene Expression Regulation / Q000187:drug effects*; D006624:Hippocampus / Q000378:metabolism* / Q000473:pathology; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism; D051605:Kv Channel-Interacting Proteins / Q000378:metabolism; D051665:Kv1.4 Potassium Channel / Q000378:metabolism; D008565:Membrane Proteins / Q000378:metabolism; D009474:Neurons / Q000145:classification / Q000166:cytology / Q000378:metabolism; D010862:Pilocarpine; D024642:Potassium Channels, Voltage-Gated / Q000235:genetics / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D051672:Shal Potassium Channels / Q000378:metabolism; D013997:Time Factors
D000076122:Disks Large Homolog 4 Protein; C501449:Dlg4 protein, rat; D047908:Intracellular Signaling Peptides and Proteins; D051605:Kv Channel-Interacting Proteins; D051665:Kv1.4 Potassium Channel; D008565:Membrane Proteins; D024642:Potassium Channels, Voltage-Gated; D051672:Shal Potassium Channels; D010862:Pilocarpine