| First Author | Murthy SR | Year | 2008 |
| Journal | J Neurochem | Volume | 106 |
| Issue | 6 | Pages | 2312-21 |
| PubMed ID | 18624921 | Mgi Jnum | J:139979 |
| Mgi Id | MGI:3810884 | Doi | 10.1111/j.1471-4159.2008.05557.x |
| Citation | Murthy SR, et al. (2008) Identification and characterization of a novel, shorter isoform of the small conductance Ca2+ -activated K+ channel SK2. J Neurochem 106(6):2312-21 |
| abstractText | 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. |
