A5017061959- Ion channel regulation and function
- Cardiac electrophysiology and arrhythmias
- Neuroscience and Neuropharmacology Research
- Ion Transport and Channel Regulation
- Genetics and Neurodevelopmental Disorders
- Barrier Structure and Function Studies
University of Naples Federico II
2020-2025
Prior studies have revealed remarkable phenotypic heterogeneity in KCNQ2-related disorders, correlated with effects on biophysical features of heterologously expressed channels. Here, we assessed phenotypes and functional properties associated KCNQ2 missense variants R144W, R144Q, R144G. We also explored vitro blockade channels carrying R144Q mutant subunits by amitriptyline.Patients were identified using the RIKEE database through clinical collaborators. Phenotypes collected a standardized...
Gain-of-function (GoF) variants in KCNT1 channels cause severe, drug-resistant forms of epilepsy. Quinidine is a known blocker, but its clinical use limited due to severe drawbacks. To identify novel blockers, homology model human was built and used screen an in-house library compounds. Among the 20 molecules selected, five (
Developmental and epileptic encephalopathies (DEEs) are neurodevelopmental diseases characterized by refractory epilepsy, distinct electroencephalographic neuroradiological features, various degrees of developmental delay. Mutations in KCNQ2, KCNQ3, and, more rarely, KCNQ5 genes encoding voltage-gated potassium channel subunits variably contributing to excitability control specific neuronal populations at stages have been associated DEEs. In the present work, clinical features two DEE...
Neuronal Kv7 channels represent important pharmacological targets for hyperexcitability disorders including epilepsy. Retigabine is the prototype activator clinically approved seizure treatment; however, severe side effects associated with long-term use have led to its market discontinuation. Building upon recently described cryoEM structure of Kv7.2 complexed retigabine and on previous structure–activity relationship studies, a small library analogues has been designed, synthesized,...
Abstract De novo variants in KCNQ2 cause neonatal onset developmental and epileptic encephalopathy ( ‐DEE; Online Mendelian Inheritance Man #613720), most often by loss‐of‐function vitro effects. In this study, we describe a DEE proband carrying recurrent de variant (c.794C>T; p.A265V) affecting the pore domain of ‐encoded Kv7.2 subunits. Whole‐cell patch‐clamp measurement mammalian heterologous expression system revealed that, when compared to wild‐type channels, channels containing...
This study describes for the first time expression and functional role of Kv7 potassium channels in blood-brain barrier. We show that opening reduces endothelial cell permeability both physiological pathological conditions via hyperpolarization membrane sealing tight junctions. Therefore, activation might be a useful strategy to treat epilepsy other neurological disorders characterized by barrier dysfunction.
Pathogenic variants in KCNQ2 and KCNQ3, paralogous genes encoding Kv7.2 Kv7.3 voltage-gated K+ channel subunits, are responsible for early‐onset developmental/epileptic disorders characterized by heterogeneous clinical phenotypes ranging from Benign Familial Neonatal Epilepsy (BFNE) to developmental epileptic encephalopathy. account the majority of pedigrees with BFNE KCNQ3 a much smaller subgroup, but reasons this imbalance remain unclear. Analysis additional is needed further clarify...