Topic: KCNQ2

The image shows the morphology of pyramidal neuron filled with biocytin during the recording from mutant cell.This study focuses on understanding the pathophysiological mechanisms of KCNQ-DEE, a severe form of neonatal epilepsy associated with variants in genes of the KCNQ family. KCNQ genes encode subunits of KV7 voltage-gated potassium channels. Each channel is formed by four subunits and particularly heterotetrametric KV7.2/KV7.3 or KV7.5/KV7.3 channels, carrying the so-called M-current, play a crucial role in modulating neuronal excitability in the central nervous system. Most pathogenic v

Kv7.2 and Kv7.3 are neuronal voltage-gated potassium channel subunits encoded by KCNQ2 and KCNQ3 genes, underlying the M-current, a slowly activating and non-inactivating current involved in neuronal excitability control. Kv7.2 mutations lead to neonatal-onset epilepsies including developmental and epileptic encephalopathies (DEE), characterized by seizures, electroencephalographic abnormalities, and developmental delay. When expressed in vitro, most Kv7.2 variants cause loss-of-function (LoF) effects. In this study, we aimed to functionally characterize a de novo KCNQ2 mutation in the pore of

Seizures arise from disruption in mechanisms that control neuronal excitability and the M-current is one such mechanism. This low-threshold potassium current modulates neuronal excitability and suppresses repetitive firing. M-channels assemble as tetramers of Kv7 subunits and mutations in the KCNQ2 gene, encoding Kv7.2, are linked to epilepsy and intellectual disabilities. Despite this common epileptogenic mechanism, understanding M-channel regulation remains limited. We identified type 1 TARPs, well-known Transmembrane AMPA-receptors Regulatory proteins, as new interactors of the Kv7.2 subuni

The oxytocin (OXT) and relaxin-3 (RLN3) signalling systems are involved in shaping social and stress-related behaviours, but the interplay of these neural networks in relevant brain regions including the ventral hippocampus dentate gyrus (vDG), is under explored. The rat vDG is strongly innervated by OXT and RLN3-containing nerve fibres, but possible interactions of these neuropeptide systems in vDG are unknown. Therefore, we investigated the influence of OXT and RLN3 signalling, separately and in combination, on rat and human vDG neurons. Multiplex in situ hybridization (ISH) identified a mod