| First Author | Sutherland ML | Year | 1999 |
| Journal | Proc Natl Acad Sci U S A | Volume | 96 |
| Issue | 5 | Pages | 2451-5 |
| PubMed ID | 10051663 | Mgi Jnum | J:53363 |
| Mgi Id | MGI:1332345 | Doi | 10.1073/pnas.96.5.2451 |
| Citation | Sutherland ML, et al. (1999) Overexpression of a Shaker-type potassium channel in mammalian central nervous system dysregulates native potassium channel gene expression. Proc Natl Acad Sci U S A 96(5):2451-5 |
| abstractText | The nervous system maintains a delicate balance between excitation and inhibition, partly through the complex interplay between voltage-gated sodium and potassium ion channels. Because K+ channel blockade or gene deletion causes hyperexcitability, it is generally assumed that increases in K+ channel gene expression should reduce neuronal network excitability. We have tested this hypothesis by creating a transgenic mouse that expresses a Shaker-type K+ channel gene. Paradoxically, we find that addition of the extra K+ channel gene results in a hyperexcitable rather than a hypoexcitable phenotype. The presence of the transgene leads to a complex deregulation of endogenous Shaker genes in the adult central nervous system as well as an increase in network excitability that includes spontaneous cortical spike and wave discharges and a lower threshold for epileptiform bursting in isolated hippocampal slices. These data suggest that an increase in K+ channel gene dosage leads to dysregulation of normal K+ channel gene expression, and it may underlie a mechanism contributing to the pathogenesis of human aneuploidies such as Down syndrome. |
