A5031451451- Ion channel regulation and function
- Pain Mechanisms and Treatments
- Cardiac electrophysiology and arrhythmias
- Ion Channels and Receptors
- Neuroscience and Neuropharmacology Research
- Receptor Mechanisms and Signaling
- Adenosine and Purinergic Signaling
- Venomous Animal Envenomation and Studies
- Ion Transport and Channel Regulation
- Hereditary Neurological Disorders
- Rabies epidemiology and control
- Neuroendocrine regulation and behavior
- Trace Elements in Health
- Neuropeptides and Animal Physiology
- Respiratory and Cough-Related Research
- Pharmacological Receptor Mechanisms and Effects
- Analytical Chemistry and Sensors
- Botulinum Toxin and Related Neurological Disorders
- Erythrocyte Function and Pathophysiology
- Caveolin-1 and cellular processes
- Cell Adhesion Molecules Research
- RNA Research and Splicing
- Nanoplatforms for cancer theranostics
- Neurobiology and Insect Physiology Research
- Cancer, Hypoxia, and Metabolism
Yale University
2010-2024
VA Connecticut Healthcare System
2008-2024
Yuxi Normal University
2024
Binzhou University
2024
Target (United States)
2024
Binzhou Medical University
2024
Guangxi Medical University
2021-2023
Dingxi City People's Hospital
2023
Jinan University
2021
Ministry of Education of the People's Republic of China
2021
Small nerve fiber neuropathy (SFN) often occurs without apparent cause, but no systematic genetic studies have been performed in patients with idiopathic SFN (I-SFN). We sought to identify a basis for I-SFN by screening biopsy-confirmed mutations the SCN9A gene, encoding voltage-gated sodium channel Na(V)1.7, which is preferentially expressed small diameter peripheral axons.Patients referred possible I-SFN, who met criteria of ≥2 SFN-related symptoms, normal strength, tendon reflexes,...
Painful peripheral neuropathy often occurs without apparent underlying cause. Gain-of-function variants of sodium channel Na(v)1.7 have recently been found in ∼30% cases idiopathic painful small-fiber neuropathy. Here, we describe mutations Na(v)1.8, another that is specifically expressed dorsal root ganglion (DRG) neurons and nerve axons, patients with Seven Na(v)1.8 were identified 9 subjects within a series 104 predominantly Three met criteria for potential pathogenicity based on...
Abstract Controlling contact resistance in organic field‐effect transistors (OFETs) is one of the major hurdles to achieve transistor scaling and dimensional reduction. In particular context ambipolar and/or light‐emitting OFETs it a difficult challenge obtain efficient injection both electrons holes from injecting electrode such as gold since semiconductors have intrinsically large band gaps resulting significant barrier heights for at least type carrier. Here, systematic control electron...
Neurons are highly polarized cells with functionally distinct axonal and somatodendritic compartments. Voltage-gated sodium channels Na v 1.2 1.6 enriched at axon initial segments (AISs) nodes of Ranvier, where they necessary for generation propagation action potentials. Previous studies using reporter proteins in unmyelinated cultured neurons suggest that an ankyrinG-binding motif within intracellular loop 2 (L2) is sufficient targeting these to the AIS, but mechanisms channel remain poorly...
Allosteric modulation provides exciting opportunities for drug discovery of enzymes, ion channels, and G protein-coupled receptors. As cation channels gated by extracellular ATP, P2X receptors have attracted wide attention as new targets. Although small molecules targeting entered into clinical trials rheumatoid arthritis, cough, pain, negative allosteric these remains largely unexplored. Here, combining X-ray crystallography, computational modeling, functional studies channel mutants, we...
Carbon monoxide (CO) is generated endogenously by the enzyme heme oxygenase. Although CO a known vasodilator, cellular signaling mechanisms are poorly understood and source of controversy. The goal present study was to investigate dilation in porcine cerebral arterioles. Data indicate that exogenous or produced potent activator large-conductance Ca2+-activated K+ (K(Ca)) channels Ca2+ spark-induced transient K(Ca) currents arteriole smooth muscle cells. In contrast, relatively poor sparks....
Background: Primary erythromelalgia is an autosomal dominant pain disorder characterized by burning and skin redness in the extremities, with onset of symptoms during first decade families whose mutations have been physiologically studied to date. Several voltage-gated Na + channel V 1.7 linked primary erythromelalgia. Recently, a new substitution 1.7/I136V has reported Taiwanese family, which appeared at later ages (9–22 years, 17 years age or 5 7 family members), relatively slow...
Background: Nociception requires transduction and impulse electrogenesis in nerve fibers which innervate the body surface, including skin. However, molecular substrates for action potential initiation nociceptors are incompletely understood. In this study, we examined expression distribution of Na + /Ca 2+ exchanger (NCX) voltage-gated sodium channel isoforms intra-epidermal free terminals. Results: Small diameter DRG neurons exhibited robust NCX2, but not NCX1 or NCX3 immunolabeling,...
Neuropathic pain is a chronic condition that often refractory to treatment with available therapies and thus an unmet medical need. We have previously shown the voltage-gated sodium channel Nav1.3 upregulated in peripheral central nervous system (CNS) of rats following nerve injury, it contributes nociceptive neuron hyperexcitability neuropathic conditions. To evaluate therapeutic potential knockdown at specific segmental level, we constructed adeno-associated viral (AAV) vector expressing...
Marked hypersensitivity to heat and mechanical (pressure) stimuli develop after a burn injury, but the neural mechanisms underlying these effects are poorly understood. In this study, we establish new mouse model of focal second-degree injury investigate molecular cellular basis for injury-induced pain. This features robust behavioral tissue-specific altered cytokine profile, absence glial activation in spinal dorsal horn. Three voltage-gated sodium channels, Na v 1.7, 1.8, 1.9,...
Abstract Voltage-gated sodium channels Na V 1.7, 1.8 and 1.9 have been the focus for pain studies because their mutations are associated with human disorders, but role of 1.6 in is less understood. In this study, we selectively knocked out dorsal root ganglion (DRG) neurons, using 1.8-Cre directed or adeno-associated virus (AAV)-Cre mediated approaches, examined specific contribution to tetrodotoxin-sensitive (TTX-S) current these neurons its neuropathic pain. We report here that contributes...
Abstract Vincristine-induced peripheral neuropathy is a common side effect of vincristine treatment, which accompanied by pain and can be dose-limiting. The molecular mechanisms that underlie vincristine-induced are not well understood. We have established an animal model to investigate pathophysiological pain. Our previous studies shown the tetrodotoxin-sensitive voltage-gated sodium channel Nav1.6 in medium-diameter dorsal root ganglion (DRG) neurons contributes maintenance allodynia. In...
Gain-of-function missense mutations of voltage-gated sodium channel NaV1.7 have been linked to the painful disorder inherited erythromelalgia. These hyperpolarize activation, slow deactivation and enhance currents evoked by ramp stimuli (ramp currents). A correlation has recently suggested between age onset erythromelalgia extent hyperpolarizing shifts in mutant activation; causing large activation early erythromelalgia, while small within second decade life. Here, we report a family with an...
Voltage-gated sodium (Na
The Nav1.7 sodium channel is preferentially expressed in nocioceptive dorsal root ganglion and sympathetic neurons. Gain-of-function mutations produce the nocioceptor hyperexcitability underlying inherited erythromelalgia, characterized most kindreds by early-age onset of severe pain. Here we describe a mutation (Nav1.7-G616R) pedigree with adult-onset pain some family members. shifts voltage-dependence fast-inactivation depolarizing direction adult-long, but not neonatal-short splicing...
Sodium channel Na(v)1.6 is essential for neuronal excitability in central and peripheral nervous systems. Loss-of-function mutations underlie motor disorders, with homozygous-null causing juvenile lethality. Phosphorylation of by the stress-induced p38 MAPK at a Pro-Gly-Ser(553)-Pro motif its intracellular loop L1 reduces current density dorsal root ganglion-derived cell line, without changing gating properties. Phosphorylated putative binding site to Nedd4 ubiquitin ligases, we hypothesized...
Voltage-dependent L-type Ca(2+) (Ca(V)1.2) channels are the principal entry pathway in arterial myocytes. Ca(V)1.2 regulate multiple vascular functions and implicated pathogenesis of human disease, including hypertension. However, molecular identity expressed myocytes myogenic arteries that pressure blood flow is unknown. Here, we cloned subunits from resistance size cerebral demonstrate contain a novel, cysteine rich N terminus derived exon 1 (termed "exon 1c"), which located within...
Cerebellar dysfunction in multiple sclerosis (MS) contributes significantly to disability, is relatively refractory symptomatic therapy, and often progresses despite treatment with disease-modifying agents. We previously observed that sodium channel Nav1.8, whose expression normally restricted the peripheral nervous system, present cerebellar Purkinje neurons a mouse model of MS (experimental autoimmune encephalomyelitis [EAE]) humans MS. Here, we tested hypothesis upregulation Nav1.8...
Abstract Stimuli‐responsive smart photosensitizer (PS) nanoassemblies that allow enhanced delivery and controlled release of PSs are promising for imaging‐guided photodynamic therapy (PDT) tumors. However, the lack high‐sensitivity spatial‐resolution signals fast washout released from tumor tissues have impeded PDT efficacy in vivo. Herein, we report targeting, redox‐responsive magnetic fluorogenic PS ( NP‐RGD ) synthesized via self‐assembly a cRGD‐ disulfide‐containing paramagnetic small...
L-type, voltage-dependent calcium (Ca(2+)) channels, ryanodine-sensitive Ca(2+) release (RyR) and large-conductance Ca(2+)-activated potassium (K(Ca)) channels comprise a functional unit that regulates smooth muscle contractility. Here, we investigated whether genetic ablation of caveolin-1 (cav-1), caveolae protein, alters spark to K(Ca) channel coupling regulation by in murine cerebral artery cells. Caveolae were abundant the sarcolemma control (cav-1(+/+)) cells but not observed...