Margatoxin and iberiotoxin, two selective potassium channel inhibitors, induce c-fos like protein and mRNA in rat organotypic dorsal striatal slices.
The isolated single organotypic slice model allows to investigate the effects of drugs and toxins on the expression of transcription factors in the striatum without dopaminergic and glutamatergic interactions. In this study the effects of margatoxin and iberiotoxin on the expression of c-fos mRNA by in situ hybridization as well as on c-fos like protein by immunohistochemistry in isolated dorsal striatum after 10 days in culture were investigated. C-fos mRNA dose-dependently increased 30 min after incubation with margatoxin and iberiotoxin. Expression of c-fos like protein was transiently detected 3h afterwards. This effect is independent from extrinsic neuronal circuitry as dopamine neurons were found to be absent in the cultured slices. It is concluded that inhibition of voltage-gated as well as calcium-activated (Slo) potassium channels leads to activation of gene transcription in striatal neurons which may trigger long-term changes in transmitter plasticity.
Saria
A
A
Department of Psychiatry, University Hospital, Innsbruck, Austria. alois.saria@uibk.ac.at
Fischer
H S
HS
Humpel
C
C
Pfattner
A
A
Schatz
D S
DS
Schuligoi
R
R
D000818:Animals; D003342:Corpus Striatum / Q000187:drug effects* / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D015640:Ion Channel Gating; D009498:Neurotoxins / Q000494:pharmacology*; D009924:Organ Culture Techniques; D010455:Peptides / Q000494:pharmacology*; D026902:Potassium Channel Blockers; D016760:Proto-Oncogene Proteins c-fos / Q000096:biosynthesis* / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics*; D051381:Rats; D012604:Scorpion Venoms
D009498:Neurotoxins; D010455:Peptides; D026902:Potassium Channel Blockers; D016760:Proto-Oncogene Proteins c-fos; D012333:RNA, Messenger; D012604:Scorpion Venoms; C077910:margatoxin; C064719:iberiotoxin