A5066687959- Ion channel regulation and function
- Neuroscience and Neuropharmacology Research
- Cannabis and Cannabinoid Research
- Nicotinic Acetylcholine Receptors Study
- Pain Mechanisms and Treatments
- Neurotransmitter Receptor Influence on Behavior
- Cardiac electrophysiology and arrhythmias
- Orthopaedic implants and arthroplasty
- Total Knee Arthroplasty Outcomes
- Orthopedic Infections and Treatments
- Receptor Mechanisms and Signaling
- Pharmacological Receptor Mechanisms and Effects
- Nitric Oxide and Endothelin Effects
- Epilepsy research and treatment
- Photoreceptor and optogenetics research
- Signaling Pathways in Disease
- Ion Channels and Receptors
- Cholinesterase and Neurodegenerative Diseases
- Coordination Chemistry and Organometallics
- Cardiac Ischemia and Reperfusion
- Plant Stress Responses and Tolerance
- Mitochondrial Function and Pathology
- Piperaceae Chemical and Biological Studies
- Prion Diseases and Protein Misfolding
- Body Contouring and Surgery
Macquarie University
2018-2023
University of Calgary
2006-2022
Alberta Children's Hospital
2015-2022
University of Leeds
2012-2013
Zero to Three
2013
Alberta Bible College
2013
Faculty (United Kingdom)
2013
University of British Columbia
1994-2005
University of Alberta
1991-1998
Fundación Juan March
1994
Abstract Objective The relationship between genetic variation in the T‐type calcium channel gene CACNA1H and childhood absence epilepsy is well established. purpose of this study was to investigate range syndromes for which variants may contribute susceptibility architecture determine electrophysiological effects these relation proposed mechanisms underlying seizures. Methods Exons 3 35 were screened 240 patients (167 unrelated) 95 control subjects by single‐stranded conformation analysis...
Potassium channels that are inhibited by internal ATP (K channels) provide a critical link between metabolism and cellular excitability. Protein kinase C (PKC) acts on K to regulate diverse processes, including cardioprotection ischemic preconditioning pancreatic insulin secretion. PKC action decreases the Hill coefficient of binding cardiac channels, thereby increasing their open probability at physiological concentrations. We show similarly regulates recombinant from both pancreas heart....
Abstract: We applied reverse transcription‐PCR to examine the gene expression of cyclic GMP (cGMP)‐dependent protein kinase in rat brain. A PCR product with size predicted from type II cGMP‐dependent (cGK II) cDNA was detected various regions brain, highest thalamus. The amplified this subcloned, sequenced, and consequently shown be cGK II. Northern analysis confirmed that highly expressed In situ hybridization riboprobes derived indicated mRNA outer layers cortex, septum, amygdala,...
Piperine, a natural compound isolated from the fruits of Piper, is known to modulate several neurotransmitter systems such as serotonin, norepinephrine, and GABA, all which have been linked development convulsions. Fruits Piper species suggested means for managing seizure disorders. The present study was designed elucidate anticonvulsant effect piperine its mechanisms action using in-silico, in-vivo in-vitro techniques.PASS software used determine possible activity mechanisms. Furthermore...
Abstract Vitamin E (VE) has been added to ultrahigh‐molecular‐weight polyethylene (UHMWPE) acetabular cups and tibial trays primarily reduce oxidative damage the polymer. The aim of this study was investigate relative wear rates UHMWPE‐containing VE compared with virgin UHMWPE. ability amount inflammatory cytokines produced from stimulated peripheral blood mononuclear cells (PBMNCs) also investigated. Stimulation achieved by exposure PBMNCs either lipoplysaccharide (LPS) or VE‐containing...
Abstract Heron and colleagues (Ann Neurol 2004;55:595–596) identified three missense mutations in the Cav3.2 T‐type calcium channel gene (CACNA1H) patients with idiopathic generalized epilepsy. None of variants were associated a specific epilepsy phenotype not found juvenile absence or childhood Here, we introduced functionally characterized these using transiently expressed human channels. Two exhibited functional changes that are consistent increased function. Taken together, findings...
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...
Low-voltage-activated (T-type) calcium channels are important regulators of the transmission nociceptive information in primary afferent pathway and finding ligands that modulate these is a key focus drug discovery field. Recently, we characterized set novel compounds with mixed cannabinoid receptor/T-type channel blocking activity examined their analgesic effects animal models pain. Here, have built on previous findings synthesized new series small organic compounds. We then screened them...
Low-voltage-activated (T-type) calcium channels play a crucial role in number of physiological processes, including neuronal and cardiac pacemaker activity nociception. Therefore, finding specific modulators and/or blockers T-type has become an important field drug discovery. One characteristic is that they share several structural similarities with voltage-gated sodium (VGSCs). We therefore hypothesized binding sites for certain channel blocking peptide toxins may be present channels. The...
THE expression of the olfactory cyclic nucleotide-gated channel (CNG1) was studied in rat brain. Using RT-PCR, levels CNG1 mRNA were determined relative to a constantly expressed gene, α-tubulin. RT-PCR showed that detectable pituitary gland, bulb, and cerebellum adult 5-day-old rats. A 3.4 kb detected bulb by Northern blotting. In situ hybridization analysis is present Purkinje cells cerebellum. studies on cell-enriched cultures obtained from 16-day-old embryos (E16) confirmed these...
Summary: Purpose: Childhood absence epilepsy (CAE) is an idiopathic form of seizure disorder that believed to have a genetic basis. Methods: We examined the biophysical consequences seven mutations in Ca v 3.2 T‐type calcium channel gene linked CAE. Results: Of variants examined, one mutants, replacement glycine 848 domain II‐S2 region with serine, resulted significant slowing time courses both activation and inactivation across wide range membrane potentials. These changes are consistent...
Cav3.2 calcium channels are important mediators of nociceptive signaling in the primary afferent pain pathway, and their expression is increased various rodent models chronic pain. Previous work from our laboratory has shown that this part mediated by an aberrant deubiquitinase USP5, which associates with these increases stability. Here, we report on a novel bioactive rhodanine compound (II-1), was identified library screens. II-1 inhibits biochemical interactions between USP5 domain III-IV...
Background and Purpose T‐type Ca channels ( I ) regulate neuronal excitability contribute to neurotransmitter release. The phytocannabinoids Δ 9 ‐tetrahydrocannabinol cannabidiol effectively modulate , but effects of other biologically active on these are unknown. We thus investigated the modulation by low abundance phytocannabinoids. Experimental Approach A fluorometric (fluorescence imaging plate reader [FLIPR]) assay was used investigate human (Ca V 3.1, 3.2 3.3) stably expressed in...
Spider venoms are rich sources of peptidic ion channel modulators with important therapeutical potential. We screened a panel 60 spider to find channels involved in pain transmission. isolated, synthesized and pharmacologically characterized Cd1a, novel peptide from the venom Ceratogyrus darlingi. Cd1a reversibly paralysed sheep blowflies (PD50 1318 pmol/g) inhibited human Cav2.2 (IC50 2.6 μM) but not Cav1.3 or Cav3.1 > 30 fluorimetric assays. In patch-clamp electrophysiological assays rat...
Voltage-gated sodium (Na<sub>v</sub>) and calcium (Ca<sub>v</sub>) channels play important roles in physiological processes, including neuronal cardiac pacemaker activity, vascular smooth muscle contraction, nociception. They are thought to share a common ancestry, and, particular, T-type (T-type) structural similarities with Na<sub>v</sub> channels, both regard membrane topology gating kinetics, rapid inactivation. We thus reasoned that certain drugs acting on may also modulate the...
N-Methyl-D-aspartate receptors (NMDARs) and α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPARs) are two major types of ionotropic glutamate involved in synaptic transmission. However, excessive activity these can be cytotoxic thus their function must precisely controlled. We have previously reported that NMDA receptor is dysregulated following genetic knockout cellular prion protein (PrPC), PrPC regulation copper-dependent. Here, we employed electrophysiological methods to study...
Abstract Synthetic cannabinoid receptor agonists (SCRAs) are new psychoactive substances associated with acute intoxication and even death. However, the molecular mechanisms through which SCRAs may exert their toxic effects remain unclear—including potential differential activation of G protein subtypes by type 1 (CB1), a major target SCRA. We measured CB1‐mediated Gα s i/o proteins examining stimulation (pertussis toxin, PTX treated) as well inhibition (non‐PTX forskolin (FSK)‐induced...