Contribution of KCNQ5 to the medium and slow afterhyperpolarization currents in hippocampal neurons

Abstract

Benign familial neonatal convulsion (BNFC) is a neurological disorder caused by mutations in the potassium channel genes KCNQ2 and KCNQ3, which contribute to the medium afterhyperpolarization current (ImAHP) and slow afterhyperpolarization current (IsAHP) in hippocampal neurons. KCNQ5 is not yet linked to any human disease but is broadly expressed in the brain similar to KCNQ2 and KCNQ3. To investigate the role of KCNQ5 in the brain we generated a KCNQ5 dominantnegative (Kcnq5dn/dn) mouse. Histological analysis did not reveal structural brain abnormalities. Western blots of total brain proteins revealed that there is no detectable influence of the mutated KCNQ5 protein on overall KCNQ2, KCNQ3 and KCNQ5 levels. In addition, the subcellular localization of KCNQ2 and KCNQ3 is not altered in Kcnq5dn/dn mice. Using electrophysiological analysis we could show that KCNQ5 contributes to the ImAHP and IsAHP in a subset of hippocampal neurons where KCNQ5 is highly expressed. Therefore, our study is a direct demonstration that in addition to KCNQ2 and KCNQ3, KCNQ5 channels contribute to the ImAHP and IsAHP.