A5020708402- Ion channel regulation and function
- Ion Channels and Receptors
- Adenosine and Purinergic Signaling
- Neuroscience and Neuropharmacology Research
- Nicotinic Acetylcholine Receptors Study
- Cardiac electrophysiology and arrhythmias
- Venomous Animal Envenomation and Studies
- Lipid Membrane Structure and Behavior
- Neuroscience and Neural Engineering
- Hearing, Cochlea, Tinnitus, Genetics
- Receptor Mechanisms and Signaling
- Neurobiology and Insect Physiology Research
- Connexins and lens biology
- Genetic Neurodegenerative Diseases
- Neuroscience of respiration and sleep
- Pain Mechanisms and Treatments
- Biochemical Analysis and Sensing Techniques
- Erythrocyte Function and Pathophysiology
- Neurological disorders and treatments
- Insect and Pesticide Research
- Organic Light-Emitting Diodes Research
- Cellular transport and secretion
- Toxin Mechanisms and Immunotoxins
- Plant and Biological Electrophysiology Studies
- Biochemical and Structural Characterization
National Institute of Neurological Disorders and Stroke
2015-2024
National Institutes of Health
2015-2024
University of Colorado Anschutz Medical Campus
2023-2024
Columbia University
2024
University of Montana
2024
Lawrence Livermore National Laboratory
2024
University of California, Davis
2023
Gwangju Institute of Science and Technology
2004-2005
Chosun University
2005
Institute of Molecular Biology and Biophysics
2005
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...
Recent evidence suggests that there may be overactivation of the N-methyl-D-aspartate (NMDA) subtype excitatory amino acid receptors in Huntington's disease (HD). Tryptophan metabolism by kynurenine pathway produces both quinolinic acid, an NMDA receptor agonist, and kynurenic antagonist. In present study, multiple components tyrosine tryptophan metabolic pathways were quantified postmortem putamen 35 control 30 HD patients, using HPLC with 16-sensor electrochemical detection. Consistent...
Abstract We previously found that quinolinic acid striatal excitotoxin lesions result in a relative sparing of somatostatin and neuropeptide Y neurons. In the present study we examined dose‐response effects excitotoxins acting at three subtypes glutamate receptors: N‐methyl‐D‐aspartate (AA1), quisqualate (AA2), kainic (AA3). Concentrations both somatostatin‐like immunoreactivity (SLI) Y‐like (NPYLI) were compared with those substance P‐like (SPLI) GABA. Kainic (AA3), quisqualic AMPA (AA2)...
The hair cell mechanotransduction (MET) channel complex is essential for hearing, yet it’s molecular identity and structure remain elusive. transmembrane channel–like 1 (TMC1) protein localizes to the site of MET channel, interacts with tip-link responsible mechanical gating, genetic alterations in TMC1 alter properties cause deafness, supporting hypothesis that forms channel. We generated a model based on X-ray cryo-EM structures TMEM16 proteins, revealing presence large cavity near...
Voltage-activated potassium (Kv) channels open to conduct K+ ions in response membrane depolarization, and subsequently enter non-conducting states through distinct mechanisms of inactivation. X-ray structures detergent-solubilized Kv appear have captured an state even though a C-type inactivated would predominate membranes the absence transmembrane voltage. However, for voltage-activated ion channel lipid bilayer environment not yet been reported. Here we report structure Kv1.2–2.1 paddle...
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...
The mechanoelectrical transduction (MET) channel in auditory hair cells converts sound into electrical signals, enabling hearing. Transmembrane-like 1 and 2 (TMC1 TMC2) are implicated forming the pore of MET channel. Here, we demonstrate that inhibition channels, breakage tip links required for MET, or buffering intracellular Ca ... induces pronounced phosphatidylserine externalization, membrane blebbing, ectosome release at cell sensory organelle, culminating loss TMC1. Membrane homeostasis...
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,...
In Kv channels, an activation gate is thought to be located near the intracellular entrance ion conduction pore. Although COOH terminus of S6 segment has been implicated in forming structure, residues positioned at occluding part remain undetermined. We use a mutagenic scanning approach Shaker channel, mutating each residue region (T469-Y485) alanine, tryptophan, and aspartate identify positions that are insensitive mutation find mutants disrupt gate. Most open steeply voltage-dependent...
Protein toxins from venomous animals exhibit remarkably specific and selective interactions with a wide variety of ion channels. Hanatoxin grammotoxin are two related protein found in the venom Chilean Rose Tarantula, Phrixotrichus spatulata . inhibits voltage-gated K + channels Ca 2+ Both inhibit their respective by interfering normal operation voltage-dependent gating mechanism. The sequence homology hanatoxin grammotoxin, as well similar mechanism action, raises possibility that they...