A5046974677- Ion channel regulation and function
- Cardiac electrophysiology and arrhythmias
- Neuroscience and Neuropharmacology Research
- Neuroscience and Neural Engineering
- Biochemical and Molecular Research
- HIV/AIDS drug development and treatment
- Blood disorders and treatments
- Colorectal Cancer Screening and Detection
- Colorectal Cancer Treatments and Studies
- Nicotinic Acetylcholine Receptors Study
- Genetic factors in colorectal cancer
- Nitric Oxide and Endothelin Effects
- Signaling Pathways in Disease
- Hepatitis B Virus Studies
- Ion Transport and Channel Regulation
- Viral Infections and Immunology Research
- Electron Spin Resonance Studies
- Hepatitis C virus research
- Click Chemistry and Applications
- Synthesis and Characterization of Heterocyclic Compounds
- Redox biology and oxidative stress
- Membrane-based Ion Separation Techniques
- Receptor Mechanisms and Signaling
- Neuroinflammation and Neurodegeneration Mechanisms
University of Alberta
2017-2024
University of British Columbia
2014-2024
La Roche College
2013
Background. Resistance to mericitabine (prodrug of HCV NS5B polymerase inhibitor PSI-6130) is rare and conferred by the S282T mutation.
Kv1.2 is a prominent voltage-gated potassium channel that influences action potential generation and propagation in the central nervous system. We explored multi-protein complexes containing using mass spectrometry followed by screening for effects on Kv1.2. report Slc7a5, neutral amino acid transporter, has profound impact Co-expression with Slc7a5 reduces total protein, dramatically hyperpolarizes voltage-dependence of activation -47 mV. These are attenuated expression Slc3a2, known...
Therapies with both immunomodulatory and neuroprotective properties are thought to have the greatest promise in reducing severity progression of multiple sclerosis (MS). Several reactive oxygen (ROS) nitrogen species (RNS) implicated inflammatory-mediated damage central nervous system (CNS) MS its animal model, experimental autoimmune encephalomyelitis (EAE). TEMPOL (4-hydroxy-2,2,6,6-tetramethylpiperidine-N-oxyl) is a stable nitroxide radical potent antioxidant activity. The goal our...
In excitable cells, ion channels are frequently challenged by repetitive stimuli, and their responses shape cellular behavior regulating the duration termination of bursts action potentials. We have investigated Shaker family voltage-gated potassium (Kv) subjected to with a particular focus on Kv1.2. Genetic deletion this subunit results in complete mortality within 2 weeks birth mice, highlighting critical physiological role for Kv1.2 exhibit unique property described previously as...
Abstract Kv1.2 is a prominent potassium channel subtype in the nervous system and serves as an important structural template for investigation of ion function. However, voltage-dependence exhibits dramatic cell-to-cell variability due to gating mode shift that regulated by unknown mechanism. We report this variable behavior extracellular redox environment. Exposure reducing agents promotes properties towards ‘inhibited’ resists opening, causes channels exhibit pronounced use-dependent...
Background: The incidence of colorectal cancer (CRC) is decreasing in individuals >50 years due to organised screening but has increased for younger individuals. We characterized symptoms and their timing before diagnosis young Methods: identified all patients diagnosed with CRC between 1990–2017 British Columbia, Canada. Individuals <50 (n = 2544, EoCRC) a matched cohort 2570, LoCRC) underwent chart review identify related at determine time from symptom onset diagnosis. Results:...
Voltage-gated potassium channels are important regulators of electrical excitation in many tissues, with Kv1.2 standing out as an essential contributor the CNS. Genetic deletion invariably leads to early lethality mice. In humans, mutations affecting function linked epileptic encephalopathy and movement disorders. We have demonstrated that is subject a unique regulatory mechanism which repetitive stimulation dramatic potentiation current. this study, we explore properties molecular...
Kv1.2 potassium channels influence excitability and action potential propagation in the nervous system. Unlike closely-related Kv1 channels, exhibits highly variable voltage-dependence of gating, attributed to regulation by unidentified extrinsic factors. Variability gating is strongly influenced extracellular redox potential, we demonstrate that currents dorsal root ganglion sensory neurons exhibit similar variability sensitivity as observed when channel heterologously expressed cell lines....
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ABSTRACT Kv1.2 potassium channels influence excitability and action potential propagation in the nervous system. Unlike closely-related Kv1 channels, exhibits highly variable voltage-dependence of gating, attributed to regulation by unidentified extrinsic factors. Variable gating is strongly influenced extracellular redox potential, we demonstrate that currents dorsal root ganglion sensory neurons exhibit similar variability sensitivity as observed when channel heterologously expressed cell...
Many voltage-dependent ion channels are regulated by accessory proteins. We recently reported powerful regulation of Kv1.2 potassium the amino acid transporter Slc7a5. In this study, we report that Kv1.1 also Slc7a5, albeit with different functional outcomes. heterologous expression systems, exhibits prominent current enhancement ('disinhibition') holding potentials more negative than −120 mV. Knockdown endogenous Slc7a5 leads to larger currents and strongly attenuates disinhibition effect,...
ABSTRACT Kv1.2 is a prominent ion channel in the CNS, where it regulates neuronal excitability. structure and function are well understood, but there less consensus on mechanisms of regulation other potassium channels by auxiliary proteins. We identified novel regulators mass spectrometry approach. The neutral amino acid transporter Slc7a5 causes dramatic hyperpolarizing shift activation. In contrast, LMAN2 recently candidate regulator that has opposite effect gating: large depolarizing...
ABSTRACT Many voltage-dependent ion channels are regulated by accessory proteins, although the underlying mechanisms and consequences often poorly understood. We recently reported a novel function of amino acid transporter Slc7a5 as powerful regulator Kv1.2 activation. In this study, we report that Kv1.1 also Slc7a5, albeit with different functional outcomes. heterologous expression systems, exhibits prominent current enhancement (‘disinhibition’) holding potentials more negative than −120...