A5002120169- Ion channel regulation and function
- Cardiac electrophysiology and arrhythmias
- Neuroscience and Neuropharmacology Research
- Neuroscience and Neural Engineering
- Advanced Memory and Neural Computing
- Signaling Pathways in Disease
- Lipid Membrane Structure and Behavior
- Semiconductor materials and devices
- Superconducting Materials and Applications
- Protein purification and stability
- Neuroblastoma Research and Treatments
- Medical Imaging Techniques and Applications
- Nanopore and Nanochannel Transport Studies
- Nicotinic Acetylcholine Receptors Study
- Neurobiology and Insect Physiology Research
- Photoreceptor and optogenetics research
- Force Microscopy Techniques and Applications
- Plant and Biological Electrophysiology Studies
- Liver Disease Diagnosis and Treatment
- Microfluidic and Bio-sensing Technologies
- Advanced Sensor Technologies Research
- RNA modifications and cancer
- Nitric Oxide and Endothelin Effects
- Metabolism, Diabetes, and Cancer
- Toxin Mechanisms and Immunotoxins
National Institute of Neurological Disorders and Stroke
2021-2024
National Institutes of Health
2019-2024
University of Wisconsin–Madison
2015-2018
University Hospital Complex Of Vigo
2018
Universitat Pompeu Fabra
2012-2016
Voltage-activated potassium (Kv) channels open upon membrane depolarization and proceed to spontaneously inactivate. Inactivation controls neuronal firing rates serves as a form of short-term memory is implicated in various human neurological disorders. Here, we use high-resolution cryo–electron microscopy computer simulations determine one the molecular mechanisms underlying this physiologically crucial process. Structures activated Shaker Kv channel its W434F mutant lipid bilayers...
Abstract The Kv1.3 potassium channel is expressed abundantly on activated T cells and mediates the cellular immune response. This role has made a target for therapeutic immunomodulation to block its activity suppress cell activation. Here, we report structures of human alone, with nanobody inhibitor, an antibody-toxin fusion blocker. Rather than directly, four copies bind tetramer’s voltage sensing domains pore domain induce inactive conformation. In contrast, docks toxin at extracellular...
Abstract The Kv2.1 voltage-activated potassium (Kv) channel is a prominent delayed-rectifier Kv in the mammalian central nervous system, where its mechanisms of activation and inactivation are critical for regulating intrinsic neuronal excitability 1,2 . Here we present structures lipid environment using cryo-electron microscopy to provide framework exploring functional how mutations causing epileptic encephalopathies 3–7 alter activity. By studying series disease-causing mutations,...
Despite the substantial knowledge on antidiabetic, antiobesity and antihypertensive actions of tungstate, information its primary target/s is scarce. Tungstate activates both ERK1/2 pathway vascular voltage- Ca2+-dependent large-conductance BKαβ1 potassium channel, which modulates smooth muscle cell (VSMC) proliferation function, respectively. Here, we have assessed possible involvement channels in tungstate-induced ERK phosphorylation relevance for VSMC proliferation. Western blot analysis...
Eukaryotic voltage-gated K + channels have been extensively studied, but the structural bases for some of their most salient functional features remain to be established. C-type inactivation, example, is an auto-inhibitory mechanism that confers temporal resolution signal-firing activity. In a recent breakthrough, studies mutant Shaker prone inactivate indicated this process entails dilation selectivity filter, narrowest part ion conduction pathway. Here, we report atomic-resolution...
Ewing sarcoma (ES) is an aggressive tumor defined by EWSR1 gene fusions that behave as oncogene. Here we demonstrate RING1B highly expressed in primary ES tumors, and its expression independent of the fusion RING1B-depleted cells display profile enriched genes functionally involved hematological development but depletion does not induce cellular differentiation. In cells, directly binds SCN8A sodium channel promoter results enhanced Nav1.6 function. The signaling pathway most significantly...
AimsTungstate reduces blood pressure in experimental animal models of both hypertension and metabolic syndrome, although the underlying mechanisms are not fully understood. Given that large-conductance voltage- Ca2+-dependent K+ (BK) channel is a key element control arterial tone, our aim was to evaluate whether BK modulation by tungstate can contribute its antihypertensive effect.
Abstract Aims To study the response of clinical variables (HbA 1c , body weight, lipid profile and blood pressure) over 24 months liraglutide treatment in a real‐world setting, to describe evolution HbA weight reduction by employing generalized additive mixed models ( GAMM s). Methods We included people aged ≥ 18 years with Type 2 diabetes mellitus that initiated between November 2011 May 2015. Demographic data were retrieved retrospectively from electronic medical records median duration...
Abstract Voltage-activated potassium (Kv) channels open upon membrane depolarization and proceed to spontaneously inactivate. Inactivation controls neuronal firing rates serves as a form of short-term memory, is implicated in various human neurological disorders. Here, we use high-resolution cryo-electron microscopy computer simulations determine one the molecular mechanisms underlying this physiologically crucial process. Structures activated Shaker Kv channel its W434F mutant lipid...