Down-regulation of BK channel expression in the pilocarpine model of temporal lobe epilepsy

• Published in: Brain research 2008-03, Vol.1200, p.116-131
• Main Authors: Pacheco Otalora, Luis F, Hernandez, Eder F, Arshadmansab, Massoud F, Francisco, Sebastian, Willis, Michael, Ermolinsky, Boris, Zarei, Masoud, Knaus, Hans-Guenther, Garrido-Sanabria, Emilio R
• Format: Article
• Language: English
• Subjects: Animals; Biological and medical sciences; Cell Membrane - chemistry; Cell Membrane - drug effects; Cell Membrane - metabolism; Cerebral Cortex - drug effects; Cerebral Cortex - metabolism; Cerebral Cortex - physiopathology; Chronic Disease; Convulsants - pharmacology; Disease Models, Animal; Down-Regulation - drug effects; Down-Regulation - physiology; Epilepsy; Epilepsy, Temporal Lobe - chemically induced; Epilepsy, Temporal Lobe - metabolism; Epilepsy, Temporal Lobe - physiopathology; Fluorescent Antibody Technique; Genetic Predisposition to Disease - genetics; Granule cell; Headache. Facial pains. Syncopes. Epilepsia. Intracranial hypertension. Brain oedema. Cerebral palsy; Hippocampus - drug effects; Hippocampus - metabolism; Hippocampus - physiopathology; Large-Conductance Calcium-Activated Potassium Channels - drug effects; Large-Conductance Calcium-Activated Potassium Channels - genetics; Large-Conductance Calcium-Activated Potassium Channels - metabolism; Medical sciences; Membrane Potentials - drug effects; Membrane Potentials - physiology; Mossy fiber; Mossy Fibers, Hippocampal - drug effects; Mossy Fibers, Hippocampal - metabolism; Muscarinic Agonists - pharmacology; Nervous system (semeiology, syndromes); Neurology; Neurons - drug effects; Neurons - metabolism; Pilocarpine; Potassium - metabolism; Presynaptic; Rats; RNA, Messenger - drug effects; RNA, Messenger - metabolism; Vesicular Glutamate Transport Protein 1 - drug effects; Vesicular Glutamate Transport Protein 1 - metabolism
• ISSN: 0006-8993; 1872-6240
• DOI: 10.1016/j.brainres.2008.01.017

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 α-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.