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Identification and characterization of a novel, shorter isoform of the small conductance Ca 2+ ‐activated K + channel SK2
Author(s) -
Murthy Saravana R. K.,
Teodorescu Georgeta,
Nijholt Ingrid M.,
Dolga Amalia M.,
Grissmer Stephan,
Spiess Joachim,
Blank Thomas
Publication year - 2008
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.2008.05557.x
Subject(s) - gene isoform , hippocampal formation , biology , western blot , neuroscience , hippocampus , electrophysiology , exon , microbiology and biotechnology , gene , biochemistry
Throughout the CNS, small conductance Ca 2+ ‐activated potassium (SK) channels modulate firing frequency and neuronal excitability. We have identified a novel, shorter isoform of standard SK2 (SK2‐std) in mouse brain which we named SK2‐sh. SK2‐sh is alternatively spliced at exon 3 and therefore lacks 140 amino acids, which include transmembrane domains S3, S4 and S5, compared with SK2‐std. Western blot analysis of mouse hippocampal tissue revealed a 47 kDa protein product as predicted for SK2‐sh along with a 64 kDa band representing the standard SK2 isoform. Electrophysiological recordings from transiently expressed SK2‐sh revealed no functional channel activity or interaction with SK2‐std. With the help of real‐time PCR, we found significantly higher expression levels of SK2‐sh mRNA in cortical tissue from AD cases when compared with age‐matched controls. A similar increase in SK2‐sh expression was induced in cortical neurons from mice by cytokine exposure. Substantial clinical evidence suggests that excess cytokines are centrally involved in the pathogenesis of Alzheimer’s disease. Thus, SK2‐sh as a downstream target of cytokines, provide a promising target for additional investigation regarding potential therapeutic intervention.