Topic: M-current

Multiple sclerosis (MS) is by far one of the most commonly occurring demyelinating neuroinflammatory diseases of young adults that is characterized by degradation of the myelin sheath of axons resulting eventually in permanent neurological deficits. Several mediators of the kallikrein-kinin system (KKS) have been identified to be critical contributors to MS pathogenesis and potent direct modulators of neurological functions. In this context, high levels of plasma prekallikrein (PK) were found in active central nervous system (CNS) lesions of MS patients. Recently, Kv7 channels that generate th

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

Understanding the intricate functionality of the cerebral cortex requires integrating local circuit properties with global brain dynamics. Our study draws insights from biophysically detailed models of spiking neurons containing specific neural mechanisms, such as M-current and adaptation currents (Dalla Porta et al. Plos Comp. Bio., 2023). We incorporated these features in a mean-field model and, using human tractography data, we constructed a virtual whole-brain model consisting of 68 cortical nodes (Goldman et al. Front. Comput. Neurosci., 2023). To enhance realism, we introduced heterogene

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