Abstract
KCNQ3 (OMIM 602232) is a voltage-gated K-channel alpha subunit mainlyexpressed in CNS neurons. KCNQ3 forms a heterotetrameric K-channel withits homolog KCNQ2, and this KCNQ2/KCNQ3 heterotetramer provides theM-current, a delayed-rectifier type persisting K-current that regulatesneuronal excitability. A recent study has identified a point missensemutation in the pore region of KCNQ3 that leads to idiopathic neonatalepilepsy BFNC2 (OMIM 121201). However, functional evidence that linksthis mutation to epileptic neuronal hyperexcitability has so far beenlacking. In this study, we examined physiological properties of themutant KCNQ3 heterologously expressed in HEK293 cells . Our results show:1) when expressed solely, mutant KCNQ3 channels were expressed onthe plasma membrane but generated no obvious current; 2) when co-expressed with KNCQ2, KCNQ2/KCNQ3 mutant channels generated a current similar to wild-type KCNQ2/KCNQ3 channels; 3) the KCNQ2/KCNQ3 mutant current had very similar activation kinetics and voltage-dependence to the wild-type KCNQ2/KCNQ3 current, but its conductance was a way smaller than the wild-type current. We conclude that this KCNQ3 mutation reduces the conductance of M-current without changing its voltage-dependent gating, and thus causes hyperexcitability of CNS neurons that leads to the BFNC2 phenotype. [Jpn J Physiol 55 Suppl:S126 (2005)]
