Topic: Kv7 channels

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

Blood-brain barrier (BBB) disruption and the consequent alteration of solute and ion transport play a pivotal role in the onset and progression of many neurological diseases, including epilepsy. Among the players that have been shown to modulate BBB function, our group recently demonstrated that Kv7 channels, a family of voltage-gated potassium channels, are critical modulators of barrier permeability, both in physiological conditions and experimental models of seizures. Accumulating evidence suggest that the renin-angiotensin system (RAS) is altered during epilepsy and affects BBB permeabilit

Dravet Syndrome is a developmental and epileptic encephalopathy, with intractable seizures and other comorbidities; due to loss of function variants in SCN1A, the disease mostly manifests because of the impairment of the functionality of inhibitory interneurons. Trying to address the unmet clinical needs of patients carrying missense variants, we used a transgenic mouse model carrying the recurrent variant p.(Ala1783Val) in Scn1a. This mouse closely recapitulates the clinical phenotype, allowing to more deeply explore the epileptogenesis and find new precision medicine approaches.We carried ou

Acetylcholine is a neurotransmitter and neuromodulator that critically modulates cognition. We have shown that acetylcholine activates axonal muscarinic receptors in hippocampal dentate gyrus granule neurons to persistently lower the action potential (AP) threshold and enhance neuronal excitability1. This was due to a sustained increase in T-type Ca2+ channel activity resulting in elevated basal Ca2+ levels which inhibited KV7 channels. The intracellular mechanism coupling axonal muscarinic receptors to T-type Ca2+ channels remains unknown. We investigated this by making electrophysiological r