![[feed]](/style/images/feed-icon-14x14.png){kind=icon}
| Item Type: | Article |
|---|---|
| Title: | Moderate loss of function of cyclic-AMP-modulated KCNQ2/KCNQ3 K+ channels causes epilepsy |
| Creators Name: | Schroeder, B.C. and Kubisch, C. and Stein, V. and Jentsch, T.J. |
| Abstract: | Epilepsy affects more than 0.5% of the world's population and has a large genetic component. It is due to an electrical hyperexcitability in the central nervous system. Potassium channels are important regulators of electrical signalling, and benign familial neonatal convulsions (BFNC), an autosomal dominant epilepsy of infancy, is caused by mutations in the KCNQ2 or the KCNQ3 potassium channel genes. Here we show that KCNQ2 and KCNQ3 are distributed broadly in brain with expression patterns that largely overlap. Expression in Xenopus oocytes indicates the formation of heteromeric KCNQ2/KCNQ3 potassium channels with currents that are at least tenfold larger than those of the respective homomeric channels. KCNQ2/KCNQ3 currents can be increased by intracellular cyclic AMP, an effect that depends on an intact phosphorylation site in the KCNQ2 amino terminus. KCNQ2 and KCNQ3 mutations identified in BFNC pedigrees compromised the function of the respective subunits, but exerted no dominant-negative effect on KCNQ2/KCNQ3 heteromeric channels. We predict that a 25% loss of heteromeric KCNQ2/KCNQ3-channel function is sufficient to cause the electrical hyperexcitability in BFNC. Drugs raising intracellular cAMP may prove beneficial in this form of epilepsy. |
| Keywords: | Amino Acid Sequence, Brain, Cultured Cells, Molecular Cloning, Cyclic AMP, Complementary DNA, Epilepsy, Gene Expression, Molecular Sequence Data, Oocytes, Point Mutation, Potassium Channels, Sequence Alignment, Tissue Distribution, Animals, Xenopus |
| Source: | Nature |
| ISSN: | 0028-0836 |
| Publisher: | Nature Publishing Group |
| Volume: | 396 |
| Number: | 6712 |
| Page Range: | 687-690 |
| Date: | 17 December 1998 |
| Official Publication: | https://doi.org/10.1038/25367 |
| PubMed: | View item in PubMed |
Repository Staff Only: item control page
