A5053937763- Ion channel regulation and function
- Neuroscience and Neuropharmacology Research
- Cardiac electrophysiology and arrhythmias
- Lipid Membrane Structure and Behavior
- Neuroscience and Neural Engineering
- Cellular transport and secretion
- Receptor Mechanisms and Signaling
- Ion Channels and Receptors
- Nicotinic Acetylcholine Receptors Study
- Ion Transport and Channel Regulation
- Photoreceptor and optogenetics research
- Diffusion and Search Dynamics
- Advanced Fluorescence Microscopy Techniques
- Spectroscopy and Quantum Chemical Studies
- Force Microscopy Techniques and Applications
- Circadian rhythm and melatonin
- Neurological disorders and treatments
- Stress Responses and Cortisol
- Biotin and Related Studies
- Advanced MRI Techniques and Applications
- Electrochemical Analysis and Applications
- Pain Mechanisms and Treatments
- Cancer Treatment and Pharmacology
- Cell Image Analysis Techniques
- Endoplasmic Reticulum Stress and Disease
University of Nevada, Reno
2021-2025
Yale University
2019-2025
VA Connecticut Healthcare System
2019-2025
Center for Neuroscience and Regenerative Medicine
2022-2024
Colorado State University
2012-2019
Junctions between cortical endoplasmic reticulum (cER) and the plasma membrane are a subtle but ubiquitous feature in mammalian cells; however, very little is known about functions molecular interactions that associated with neuronal ER-plasma-membrane junctions. Here, we report Kv2.1 (also as KCNB1), primary delayed-rectifier K(+) channel brain, induces formation of localizes to dense, cell-surface clusters contain non-conducting channels, indicating they have function unrelated...
Voltage-gated K(+) (Kv) channels regulate membrane potential in many cell types. Although the channel surface density and location must be well controlled, little is known about Kv delivery retrieval on surface. The Kv2.1 localizes to micron-sized clusters neurons transfected human embryonic kidney (HEK) cells, where it nonconducting. Because postulated involved soluble N-ethylmaleimide-sensitive factor attachment protein receptor-mediated fusion, we examined hypothesis that these are...
Stochastic motion on the surface of living cells is critical to promote molecular encounters that are necessary for multiple cellular processes. Often complexity cell membranes leads anomalous diffusion, which under certain conditions it accompanied by non-ergodic dynamics. Here, we unravel two manifestations ergodicity breaking in dynamics membrane proteins somatic hippocampal neurons. Three different tagged molecules studied soma: voltage-gated potassium and sodium channels Kv1.4 Nav1.6...
During axonal maturation, voltage-gated sodium (Nav) channels accumulate at the axon initial segment (AIS) high concentrations. This localization is necessary for efficient initiation of action potentials. The mechanisms underlying channel trafficking to AIS during development have remained elusive due a lack Nav reagents suitable resolution imaging located specifically on cell surface. Using an optical pulse-chase approach in combination with novel Nav1.6 construct containing extracellular...
The microtubule-stabilizing chemotherapy drug paclitaxel (PTX) causes dose-limiting chemotherapy-induced peripheral neuropathy (CIPN), which is often accompanied by pain. Among the multifaceted effects of PTX an increased expression sodium channel Nav1.7 in rat and human sensory neurons, enhancing their excitability. However, mechanisms underlying this have not been explored, treatment on dynamics trafficking localization channels axons possible to investigate date. In study we used a...
Sodium channel Na V 1.7 controls firing of nociceptors, and its role in human pain has been validated by genetic functional studies. However, little is known about trafficking or membrane distribution along sensory axons, which can be a meter more length. We show here with single-molecule resolution the first live visualization channels dorsal root ganglia neurons, including long-distance microtubule-dependent vesicular transport Rab6A-containing vesicles. demonstrate nanoclusters that...
Pulmonary arterial (PA) smooth muscle cells (PASMC) generate vascular tone in response to agonists coupled Gq-protein receptor signaling. Such stimulate oscillating calcium waves, the frequency of which drives strength contraction. These Ca2+ events are modulated by a variety ion channels including voltage-gated (CaV1.2), Tmem16a or Anoctamin-1 (ANO1)-encoded calcium-activated chloride (CaCC) channel, and release from sarcoplasmic reticulum through inositol-trisphosphate receptors (IP3R)....
Protein and lipid nanodomains are prevalent on the surface of mammalian cells. In particular, it has been recently recognized that ion channels assemble into nanoclusters in soma cultured neurons. However, interactions these molecules with display a considerable degree heterogeneity. Here, we investigate this heterogeneity develop statistical tools based recurrence individual trajectories to identify subpopulations within neuronal surface. We specifically study dynamics ${\mathrm{K}}^{+}$...
In mammalian cells, the cortical endoplasmic reticulum (cER) is a network of tubules and cisterns that lie in close apposition to plasma membrane (PM). We provide evidence PM domains enriched underlying cER function as trafficking hubs for insertion removal proteins HEK 293 cells. By simultaneously visualizing various transmembrane protein cargoes with total internal reflectance fluorescence microscopy, we demonstrate majority exocytotic delivery events recycled or being delivered first time...
Neuronal excitability relies on coordinated action of functionally distinction channels. Voltage-gated sodium (Na<sub>V</sub>) and potassium (K<sub>V</sub>) channels have distinct but complementary roles in firing potentials: Na<sub>V</sub> provide depolarizing current while K<sub>V</sub> hyperpolarizing current. Mutations dysfunction multiple underlie disorders excitability, including pain epilepsy. Modulating ion channel trafficking may offer a potential therapeutic strategy for these...
Na v 1.6 ( SCN8A ) is a major voltage-gated sodium channel in the mammalian CNS, and highly concentrated at axon initial segment (AIS). As previously demonstrated, microtubule associated protein MAP1B binds cytoplasmic N terminus of 1.6, this interaction disrupted by mutation p.VAVP(77–80)AAAA. We now demonstrate that results WT expression levels on somatic surface but reduced AIS cultured rat embryonic hippocampal neurons from both sexes. The binding domain did not impair vesicular...
Genetic and functional studies have confirmed an important role for the voltage-gated sodium channel Nav1.9 in human pain disorders. However, low expression of heterologous systems ( e.g. embryonic kidney 293 (HEK293) cells) has hampered its biophysical pharmacological properties development high-throughput assays drug targeting this channel. The mechanistic basis level currents is not understood. Here, we implemented a multidisciplinary approach to investigate mechanisms that govern...
Genetic and functional studies have confirmed an important role for the voltage-gated sodium channel Nav1.9 in human pain disorders. However, low expression of heterologous systems (e.g. embryonic kidney 293 (HEK293) cells) has hampered its biophysical pharmacological properties development high-throughput assays drug targeting this channel. The mechanistic basis level currents is not understood. Here, we implemented a multidisciplinary approach to investigate mechanisms that govern...