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Surface expression and single channel properties of KCNQ2/KCNQ3, M-type K+ channels involved in epilepsy

Item Type:Article
Title:Surface expression and single channel properties of KCNQ2/KCNQ3, M-type K+ channels involved in epilepsy
Creators Name:Schwake, M. and Pusch, M. and Kharkovets, T. and Jentsch, T.J.
Abstract:Mutations in either KCNQ2 or KCNQ3 underlie benign familial neonatal convulsions (BFNC), an inherited epilepsy. The corresponding proteins are co-expressed in broad regions of the brain and associate to heteromeric K(+) channels. These channels mediate M-type currents that regulate neuronal excitability. We investigated the basis for the increase in currents seen after co-expressing these subunits in Xenopus oocytes. Noise analysis and single channel recordings revealed a conductance of approximately 18 pS for KCNQ2 and approximately 7 pS for KCNQ3. Different conductance levels (ranging from 8 to 22 pS) were seen upon co-expression. Their weighted average is close to that obtained by noise analysis (16 pS). The open probability of heteromeric channels was not increased significantly. Co-expression of both subunits increased the surface expression of KCNQ2 and KCNQ3 by factors of 5 and >10, respectively. A KCNQ2 mutant associated with BFNC that has a truncated cytoplasmic carboxyl terminus did not reach the surface and failed to stimulate KCNQ3 surface expression. By contrast, several BFNC-associated missense mutations in KCNQ2 or KCNQ3 did not alter their surface expression. Thus, the increase in currents seen upon co-expressing KCNQ2 and KCNQ3 is predominantly due to an increase in surface expression, which is dependent on an intact carboxyl terminus.
Keywords:Epilepsy, Gene Expression Regulation, Ion Channel Gating, KCNQ2 Potassium Channel, KCNQ3 Potassium Channel, Mutation, Patch-Clamp Techniques, Voltage-Gated Potassium Channels, Animals
Source:Journal of Biological Chemistry
ISSN:0021-9258
Publisher:American Society for Biochemistry and Molecular Biology (U.S.A.)
Volume:275
Number:18
Page Range:13343-13348
Date:5 May 2000
Official Publication:https://doi.org/10.1074/jbc.275.18.13343
PubMed:View item in PubMed

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