Back to Search
Start Over
Hyper-SUMOylation of the Kv7 Potassium Channel Diminishes the M-Current Leading to Seizures and Sudden Death.
- Source :
-
Neuron . Sep2014, Vol. 83 Issue 5, p1159-1171. 13p. - Publication Year :
- 2014
-
Abstract
- Summary Sudden unexplained death in epilepsy (SUDEP) is the most common cause of premature mortality in epilepsy and was linked to mutations in ion channels; however, genes within the channel protein interactome might also represent pathogenic candidates. Here we show that mice with partial deficiency of Sentrin/SUMO-specific protease 2 (SENP2) develop spontaneous seizures and sudden death. SENP2 is highly enriched in the hippocampus, often the focus of epileptic seizures. SENP2 deficiency results in hyper-SUMOylation of multiple potassium channels known to regulate neuronal excitability. We demonstrate that the depolarizing M-current conducted by Kv7 channel is significantly diminished in SENP2-deficient hippocampal CA3 neurons, primarily responsible for neuronal hyperexcitability. Following seizures, SENP2-deficient mice develop atrioventricular conduction blocks and cardiac asystole. Both seizures and cardiac conduction blocks can be prevented by retigabine, a Kv7 channel opener. Thus, we uncover a disease-causing role for hyper-SUMOylation in the nervous system and establish an animal model for SUDEP. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 08966273
- Volume :
- 83
- Issue :
- 5
- Database :
- Academic Search Index
- Journal :
- Neuron
- Publication Type :
- Academic Journal
- Accession number :
- 97840791
- Full Text :
- https://doi.org/10.1016/j.neuron.2014.07.042