title: Surface expression and single channel properties of KCNQ2/KCNQ3, M-type K+ channels involved in epilepsy.
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.
authors.affiliation: Zentrum für Molekulare Neurobiologie Hamburg (ZMNH), Universität Hamburg, Martinistrasse 85, D-20246 Hamburg, Germany.
authors.forename: M
authors.initials: M
authors.lastname: Schwake
authors.forename: M
authors.initials: M
authors.lastname: Pusch
authors.forename: T
authors.initials: T
authors.lastname: Kharkovets
authors.forename: T J
authors.initials: TJ
authors.lastname: Jentsch
mesh_terms: D000818:Animals; D004827:Epilepsy / Q000503:physiopathology*; D005786:Gene Expression Regulation; D006801:Humans; D015640:Ion Channel Gating / Q000235:genetics; D051658:KCNQ2 Potassium Channel; D051659:KCNQ3 Potassium Channel; D009154:Mutation; D018408:Patch-Clamp Techniques; D015221:Potassium Channels / Q000502:physiology*; D024642:Potassium Channels, Voltage-Gated
chemical_list: D051658:KCNQ2 Potassium Channel; C496914:KCNQ2 protein, human; D051659:KCNQ3 Potassium Channel; C496916:KCNQ3 protein, human; D015221:Potassium Channels; D024642:Potassium Channels, Voltage-Gated