title: Down-regulation of BK channel expression in the pilocarpine model of temporal lobe epilepsy.
abstract: In the hippocampus, BK channels are preferentially localized in presynaptic glutamatergic terminals including mossy fibers where they are thought to play an important role regulating excessive glutamate release during hyperactive states. Large conductance calcium-activated potassium channels (BK, MaxiK, Slo) have recently been implicated in the pathogenesis of genetic epilepsy. However, the role of BK channels in acquired mesial temporal lobe epilepsy (MTLE) remains unknown. Here we used immunohistochemistry, laser scanning confocal microscopy (LSCM), Western immunoblotting and RT-PCR to investigate the expression pattern of the alpha-pore-forming subunit of BK channels in the hippocampus and cortex of chronically epileptic rats obtained by the pilocarpine model of MTLE. All epileptic rats experiencing recurrent spontaneous seizures exhibited a significant down-regulation of BK channel immunostaining in the mossy fibers at the hilus and stratum lucidum of the CA3 area. Quantitative analysis of immunofluorescence signals by LSCM revealed a significant 47% reduction in BK channel immunofluorescent signals in epileptic rats when compared to age-matched non-epileptic control rats. These data correlate with a similar reduction in BK channel protein levels and transcripts in the cortex and hippocampus. Our data indicate a seizure-related down-regulation of BK channels in chronically epileptic rats. Further functional assays are necessary to determine whether altered BK channel expression is an acquired channelopathy or a compensatory mechanism affecting the network excitability in MTLE. Moreover, seizure-mediated BK down-regulation may disturb neuronal excitability and presynaptic control at glutamatergic terminals triggering exaggerated glutamate release and seizures.
authors.affiliation: Department of Biological Sciences at the University of Texas at Brownsville/Texas Southmost College, 80 Fort Brown, Brownsville, Texas 78520, USA.
authors.forename: Luis F
authors.initials: LF
authors.lastname: Pacheco Otalora
authors.forename: Eder F
authors.initials: EF
authors.lastname: Hernandez
authors.forename: Massoud F
authors.initials: MF
authors.lastname: Arshadmansab
authors.forename: Sebastian
authors.initials: S
authors.lastname: Francisco
authors.forename: Michael
authors.initials: M
authors.lastname: Willis
authors.forename: Boris
authors.initials: B
authors.lastname: Ermolinsky
authors.forename: Masoud
authors.initials: M
authors.lastname: Zarei
authors.forename: Hans-Guenther
authors.initials: HG
authors.lastname: Knaus
authors.forename: Emilio R
authors.initials: ER
authors.lastname: Garrido-Sanabria
mesh_terms: D000818:Animals; D002462:Cell Membrane / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology; D002908:Chronic Disease; D003292:Convulsants / Q000494:pharmacology; D004195:Disease Models, Animal; D015536:Down-Regulation / Q000187:drug effects / Q000502:physiology*; D004833:Epilepsy, Temporal Lobe / Q000139:chemically induced / Q000378:metabolism* / Q000503:physiopathology; D005455:Fluorescent Antibody Technique; D020022:Genetic Predisposition to Disease / Q000235:genetics; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism* / Q000503:physiopathology; D051036:Large-Conductance Calcium-Activated Potassium Channels / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D019599:Mossy Fibers, Hippocampal / Q000187:drug effects / Q000378:metabolism; D018721:Muscarinic Agonists / Q000494:pharmacology; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D010862:Pilocarpine; D011188:Potassium / Q000378:metabolism; D012333:RNA, Messenger / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D050598:Vesicular Glutamate Transport Protein 1 / Q000187:drug effects / Q000378:metabolism
chemical_list: D003292:Convulsants; D051036:Large-Conductance Calcium-Activated Potassium Channels; D018721:Muscarinic Agonists; D012333:RNA, Messenger; C493466:Slc17a7 protein, rat; D050598:Vesicular Glutamate Transport Protein 1; D010862:Pilocarpine; D011188:Potassium