A5029443905- Ion channel regulation and function
- Pain Mechanisms and Treatments
- Neuroscience and Neuropharmacology Research
- Nonlinear Dynamics and Pattern Formation
- nanoparticles nucleation surface interactions
- Nicotinic Acetylcholine Receptors Study
- Theoretical and Computational Physics
- Spectroscopy and Quantum Chemical Studies
- stochastic dynamics and bifurcation
- Advanced Chemical Physics Studies
- Ion Channels and Receptors
- Cardiac electrophysiology and arrhythmias
- Advanced Thermodynamics and Statistical Mechanics
- Neuroinflammation and Neurodegeneration Mechanisms
- Dendrimers and Hyperbranched Polymers
- Neuropeptides and Animal Physiology
- Exercise and Physiological Responses
- MicroRNA in disease regulation
- Neurogenetic and Muscular Disorders Research
- Photochemistry and Electron Transfer Studies
- Advanced biosensing and bioanalysis techniques
- Slime Mold and Myxomycetes Research
- Quantum chaos and dynamical systems
- Chaos control and synchronization
- Receptor Mechanisms and Signaling
Ottawa Hospital
2019-2025
Carleton University
2014-2025
Ottawa Hospital Research Institute
2019-2024
National Institute of Neurological Disorders and Stroke
2022-2023
Universidade Federal de Minas Gerais
2022
University of Ottawa
2019
University of Toronto
2011-2016
Hospital for Sick Children
2011-2016
University of Calgary
2014
Institut de Génomique Fonctionnelle
2014
The mammalian spinal cord functions as a community of cell types for sensory processing, autonomic control, and movement. While animal models have advanced our understanding cellular diversity, characterizing human biology directly is important to uncover specialized features basic function pathology. Here, we present taxonomy the adult using single-nucleus RNA sequencing with spatial transcriptomics antibody validation. We identified 29 glial clusters 35 neuronal clusters, organized...
Glutamate release from rod photoreceptors is dependent on a sustained calcium influx through L-type channels. Missense mutations in the CACNA1F gene patients with incomplete X-linked congenital stationary night blindness implicate Ca v 1.4 channel subtype. Here, we describe functional and pharmacological properties of transiently expressed human shown to encode dihydropyridine-sensitive unusually slow inactivation kinetics that are not affected by either ions or coexpression ancillary β...
Background and purpose: SKF96365 (SKF), originally identified as a blocker of receptor‐mediated calcium entry, is widely used diagnostically, transient receptor potential canonical type (TRPC) channels. While SKF has been tool to define the functional roles TRPC channels in various cell tissue types, there are notable overlapping physiological pathophysiological associations between low‐voltage‐activated (LVA) T‐type The activity against Ca not previously explored, here we systematically...
Scanning tunneling microscopy data revealed the atomic processes in propagating reaction fronts that occur catalytic oxidation of hydrogen on Pt(111). The were also characterized mesoscopic length scales with respect to their velocity and width. Simulations basis a reaction-diffusion model reproduce experimental findings qualitatively well. quantitative comparison reveals limitations this traditional approach modeling spatiotemporal pattern formation nonlinear dynamics.
T-type voltage-gated calcium channels are expressed in the dendrites of many neurons, although their functional interactions with postsynaptic receptors and contributions to synaptic signaling not well understood. We combine electrophysiological ultrafast two-photon imaging demonstrate that mGluR1 activation potentiates cerebellar Purkinje cell Ca v 3.1 currents via a G-protein- tyrosine-phosphatase-dependent pathway. Immunohistochemical electron microscopic investigations on wild-type gene...
The composition of the postsynaptic ionotropic receptors that receive presynaptically released transmitter is critical not only for transducing and integrating electrical signals but also coordinating downstream biochemical signaling pathways. At glutamatergic synapses in adult CNS an overwhelming body evidence indicates NMDA receptor (NMDAR) component synaptic responses dominated by NMDARs containing GluN2A subunit, while GluN2B, GluN2C, or GluN2D play minor roles transmission. Here, we...
Dysregulated excitability within the spinal dorsal horn is a critical mediator of chronic pain. In rodent nerve injury model neuropathic pain, BDNF-mediated loss inhibition (disinhibition) gates potentiation excitatory GluN2B N-methyl-d-aspartate receptor (NMDAR) responses at lamina I synapses. However, centrality this mechanism across pain states and species, as well molecular linker involved, remain unknown. Here, we show that KCC2-dependent disinhibition coupled to increased...
The prevalence and severity of many chronic pain syndromes differ across sex, recent studies have identified differences in immune signalling within spinal nociceptive circuits as a potential mediator. Although it has been proposed that sex-specific mechanisms converge once they reach neurons the superficial dorsal horn, direct investigations using rodent human preclinical models lacking. Here, we discovered Freund's adjuvant vivo model inflammatory pain, where both male female rats display...
Animal peptide toxins have become powerful tools to study structure-function relationships and physiological roles of voltage-activated Ca<sup>2+</sup> channels. In the present study, we investigated effects PnTx3-6, a neurotoxin purified from venom spider <i>Phoneutria nigriventer</i> on cloned mammalian channels expressed in human embryonic kidney 293 cells endogenous N18 neuroblastoma cells. Whole-cell patch-clamp measurements indicate that PnTx3-6 reversibly inhibited...
Among heterogeneously catalyzed chemical reactions, the CO oxidation on Pt(110) surface under vacuum conditions offers probably greatest wealth of spontaneous formation spatial patterns. Spirals, fronts, and solitary pulses were detected at low temperatures (T<500 K), in line with standard phenomenology bistable, excitable, oscillatory reaction-diffusion systems. At high (T greater, similar 540 more surprising features like turbulence standing waves appeared experiments. Herein, we study a...
The transition between rotating spirals and spatiotemporal chaos (``spiral turbulence'') in an excitable reaction-diffusion system is investigated by means of statistics topological defects the concentration field. ratio variance mean value number show a significant deviation from unity at this point. A change defect dynamics within turbulent regime reveals strong similarity to liquid-to-gas transition, while liquid-solid-like occurs upon jumplike return region spiral stability.
Voltage-gated ion channels are implicated in pain sensation and transmission signaling mechanisms within both peripheral nociceptors the spinal cord. Genetic knockdown knockout experiments have shown that specific channel isoforms, including NaV1.7 NaV1.8 sodium CaV3.2 T-type calcium channels, play distinct pronociceptive roles. We rationally designed synthesized a novel small organic compound (Z123212) modulates recombinant native currents by selectively stabilizing their slow-inactivated...
Adsorbates with attractive lateral interactions between molecules in the presence of adsorption and thermal desorption are considered. We show that a sufficiently strong nonequilibrium reaction or process photoinduced can destabilize uniform stationary phases adsorbates lead to microstructures whose wavelength is typically shorter than diffusion length may hence be on micrometer nanometer scale. Despite their small sizes, such not destroyed by internal statistical fluctuations.
Pyrethroids are commonly used insecticides for both household and agricultural applications. It is generally reported that voltage-gated sodium channels the primary target toxicity of these chemicals to humans. The phylogenetic structural relatedness between voltagegated calcium (Ca) prompted us examine effects type 1 pyrethroid allethrin on three major classes mammalian exogenously expressed in human embryonic kidney 293 cells. We report all targets at concentrations very similar those...
Abstract Episodic ataxia type 2 (EA2) is an autosomal dominant condition characterized by paroxysmal attacks of ataxia, vertigo, and nausea, typically lasting minutes to days in duration. These symptoms can be prevented or significantly attenuated the oral administration acetazolamide; however, mechanism which acetazolamide ameliorates EA2 unknown. results from nonsense mutations CACNA1A gene that encodes α 1A (Ca v 2.1) subunit P/Q‐type calcium 2+ ) channel. We have identified a novel...
The corticotropin-releasing factor (CRF) peptides CRF and uro-cortins 1 to 3 are crucial regulators of mammalian stress inflammatory responses, they also implicated in disorders such as anxiety, depression, drug addiction. There is considerable interest the physiological mechanisms by which receptors mediate their widespread effects, here we report that native receptor (CRFR1) endogenous human embryonic kidney 293 cells can functionally couple Ca<sub>V</sub>3.2 T-type calcium channels....
T-type voltage-gated calcium channels are an emerging therapeutic target for neurological disorders including epilepsy and pain. Inhibition of reduces the excitability peripheral nociceptive sensory neurons reverses pain hypersensitivity in male rodent models. However, administration peripherally restricted antagonists failed to show efficacy multiple clinical preclinical trials, suggesting that inhibition alone may be insufficient relief.We utilized selective CNS-penetrant channel...
Abstract Prevailing safety guidance for the transportation of liquefied natural gas (LNG) is based on petroleum (LPG) transportation; therefore, considerations LNG and LPG transport must be compared. A literature review was performed to understand compare development research into LPG, their transportation, involved. The revealed key hazard differences, as well lack studies compared vast field both substances. With scientific background established, chemical physical properties are compared,...
Abstract The Ca V 3.2 isoform of T-type voltage-gated calcium channels plays a crucial role in regulating the excitability nociceptive neurons; endogenous molecules that modulate its activity, however, remain poorly understood. Here, we used serum proteomics and patch-clamp physiology to discover novel peptide albumin (1-26) facilitates channel gating by chelating trace metals tonically inhibit via H191 residue. Importantly, also potently modulated T-currents human rodent dorsal root...
Loss of GABAergic and glycinergic inhibitory efficacy in the spinal dorsal horn is associated with neuropathic pain opioid-induced hyperalgesia rodent models. Downregulation KCC2 chloride extrusion transporter a key mechanism underlying this decreased efficacy, but to-date there no evidence supporting or opposing hypothesis humans. Here we demonstrate that expression superficial neurons organ donors who died documented history pain, long-term opioid use. We show profoundly membrane primary...