Transcriptional Control ofKCNQChannel Genes and the Regulation of Neuronal Excitability
| Autor: | Mariusz Mucha, Pawel M. Mordaka, Carine Dalle, Brian D. Robertson, John E. Linley, Lezanne Ooi, Ian C. Wood, Nikita Gamper |
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| Rok vydání: | 2010 |
| Předmět: |
Transcriptional Activation
Sensory Receptor Cells Sp1 Transcription Factor Pain Repressor Biology Article Cell Line KCNQ3 Potassium Channel Cell Line Tumor Neural Pathways Transcriptional regulation Animals Humans KCNQ2 Potassium Channel Premovement neuronal activity RNA Messenger Gene Transcription factor Membrane potential Sp1 transcription factor Epilepsy General Neuroscience Neural Inhibition Potassium channel Rats Up-Regulation Repressor Proteins Gene Expression Regulation Chronic Disease Neuroscience |
| Zdroj: | The Journal of Neuroscience. 30:13235-13245 |
| ISSN: | 1529-2401 0270-6474 |
| Popis: | Regulation of the resting membrane potential and the repolarization of neurons are important in regulating neuronal excitability. The potassium channel subunits Kv7.2 and Kv7.3 play a key role in stabilizing neuronal activity. Mutations inKCNQ2andKCNQ3, the genes encoding Kv7.2 and Kv7.3, cause a neonatal form of epilepsy, and activators of these channels have been identified as novel antiepileptics and analgesics. Despite the observations that regulation of these subunits has profound effects on neuronal function, almost nothing is known about the mechanisms responsible for controlling appropriate expression levels. Here we identify two mechanisms responsible for regulatingKCNQ2andKCNQ3mRNA levels. We show that the transcription factor Sp1 activates expression of bothKCNQ2andKCNQ3, whereas the transcriptional repressor REST (repressor element 1-silencing transcription factor) represses expression of both of these genes. Furthermore, we show that transcriptional regulation ofKCNQgenes is mirrored by the correlated changes in M-current density and excitability of native sensory neurons. We propose that these mechanisms are important in the control of excitability of neurons and may have implications in seizure activity and pain. |
| Databáze: | OpenAIRE |
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