The KCNQ5 potassium channel mediates a component of the afterhyperpolarization current in mouse hippocampus

ANASTASSIOS V. TZINGOUNIS; MATTHIAS HEIDENREICH; TATJANA KHARKOVETS; GUILLERMO SPITZMAUL; HENRIK S. JENSEN; ROGER A. NICOLL; THOMAS J. JENTSCH

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

NATL ACAD SCIENCES

Lugar: Washington, DC; Año: 2010 vol. 107 p. 12232 - 12237

0027-8424

Mutations in KCNQ2 and KCNQ3 voltage-gated potassium channelslead to neonatal epilepsy as a consequence of their key role inregulating neuronal excitability. Previous studies in the brain havefocused primarily on theseKCNQ familymembers, which contributeto M-currents and afterhyperpolarization conductances in multiplebrain areas. In contrast, the function of KCNQ5 (Kv7.5), which alsodisplays widespread expression in the brain, is entirely unknown.Here, we developed mice that carry a dominant negative mutationin theKCNQ5pore to probe whetherit has a similar function as otherKCNQ channels. This mutation renders KCNQ5dn-containing homomericand heteromeric channels nonfunctional. We find thatKcnq5dn/dn mice are viable and have normal brain morphology. Furthermore,expression and neuronal localization of KCNQ2 andKCNQ3 subunits are unchanged. However, in the CA3 area of hippocampus,a region that highly expresses KCNQ5 channels, the mediumand slow afterhyperpolarization currents are significantlyreduced. In contrast, neither current is affected in the CA1 area ofthe hippocampus, a region with low KCNQ5 expression. Our resultsdemonstrate that KCNQ5 channels contribute to the afterhyperpolarizationcurrents in hippocampus in a cell type-specific manner.