| Autor: |
Jessica Hunter, Snezana Maljevic, Anupama Shankar, Anne Siegel, Barbara Weissman, Philip Holt, Larry Olson, Holger Lerche, Andrew Escayg |
| Jazyk: |
angličtina |
| Rok vydání: |
2006 |
| Předmět: |
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| Zdroj: |
Neurobiology of Disease, Vol 24, Iss 1, Pp 194-201 (2006) |
| Druh dokumentu: |
article |
| ISSN: |
1095-953X |
| DOI: |
10.1016/j.nbd.2006.06.011 |
| Popis: |
Benign familial neonatal convulsions (BFNC) is an epileptic disorder caused by dominant mutations in the genes KCNQ2 and KCNQ3 encoding the K+ channels KV7.2 and KV7.3. We identified two novel KCNQ2 mutations in two BFNC families. One mutation predicted a truncated protein (S247X) that lacks the channel's pore region, the other resulted in the amino acid substitution S122L in the S2 segment of KV7.2. In comparison to wild-type (WT) KV7.2, functional analysis of S122L mutant channels in Xenopus oocytes revealed a significant positive shift and increased slope of the activation curve leading to significant current reduction in the subthreshold range of an action potential (75% reduction at −50 mV). Our results establish an important role of the KV7.2 S2 segment in voltage-dependent channel gating and demonstrate in a human disease that subthreshold voltages are likely to represent the physiologically relevant range for this K+ channel to regulate neuronal firing. |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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