Lack of potassium current in W309R mutant KCNQ3 channel causing benign familial neonatal convulsions (BFNC)

Department of Neurology, Fukushima Medical University, School of Medicine, Fukushima, Japan.
Epilepsy research (Impact Factor: 2.02). 02/2009; 84(1):82-5. DOI: 10.1016/j.eplepsyres.2008.12.003
Source: PubMed


BFNC is an autosomal dominant epileptic disorder caused by mutations of KCNQ2 or KCNQ3 potassium channel gene. W309R missense mutation in KCNQ3 gene was previously reported in a family with BFNC. In this study, potassium currents were recorded from HEK293 cells expressing both W309R mutant KCNQ3 and wild type KCNQ2 channels. We found a lack of potassium current in W309R mutant KCNQ3 and KCNQ2 channels, which can explain the hyper-excitability of CNS in patients with BFNC.

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Available from: Shinichi Hirose
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    • "All missense mutations and functional consequences have been studied for five of them; four of them (p.Glu299Lys, p.Asp305Gly, p.Trp309Arg, and p.Gly310Val) are located in the pore region of Q3 and the fifth one (p.Arg330Cys) immediately before S6. Functional analyses in Xenopus oocytes showed that Q3 subunits carrying the p.Gly310Val and p.Asp305Gly mutation caused a 20% and 40% reduction, respectively , in the maximal current of heteromeric Q2/Q3 channels [Schroeder et al., 1998; Singh et al., 2003], whereas the Q3 p.Trp309Arg mutation was found to reduce by over 60% the Q2/Q3 heteromeric channel currents in HEK293 cells, suggesting a dominant negative effect [Uehara et al., 2008; Sugiura et al., 2009]. "
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