کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
3071102 1580750 2006 8 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Subthreshold changes of voltage-dependent activation of the KV7.2 channel in neonatal epilepsy
موضوعات مرتبط
علوم زیستی و بیوفناوری علم عصب شناسی عصب شناسی
پیش نمایش صفحه اول مقاله
Subthreshold changes of voltage-dependent activation of the KV7.2 channel in neonatal epilepsy
چکیده انگلیسی

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.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Neurobiology of Disease - Volume 24, Issue 1, October 2006, Pages 194–201
نویسندگان
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