A5031725155- Neuroscience and Neuropharmacology Research
- Ion channel regulation and function
- Neural dynamics and brain function
- Receptor Mechanisms and Signaling
- Pharmacological Receptor Mechanisms and Effects
- Photoreceptor and optogenetics research
- Nicotinic Acetylcholine Receptors Study
- Adenosine and Purinergic Signaling
- Advanced Memory and Neural Computing
- RNA Interference and Gene Delivery
- Neuroscience and Neural Engineering
- Neuroinflammation and Neurodegeneration Mechanisms
- Hearing, Cochlea, Tinnitus, Genetics
- Cellular transport and secretion
- Neonatal Respiratory Health Research
- Sleep and Wakefulness Research
- Ion Transport and Channel Regulation
- Retinal Development and Disorders
- Lipid Membrane Structure and Behavior
- Nitric Oxide and Endothelin Effects
- Cancer-related Molecular Pathways
- Cardiovascular Disease and Adiposity
- Epilepsy research and treatment
- Thermoregulation and physiological responses
- Amino Acid Enzymes and Metabolism
University College London
2000-2023
University of Ottawa
2013-2021
Ottawa Hospital
2011-2019
Ottawa Hospital Research Institute
2013-2019
McGill University
2006-2011
University of Leicester
1991-2006
The University of Western Australia
1983
Sigma-1 receptors (σ-1Rs) are endoplasmic reticulum resident chaperone proteins implicated in many physiological and pathological processes the CNS. A striking feature of σ-1Rs is their ability to interact modulate a large number voltage- ligand-gated ion channels at plasma membrane. We have reported previously that agonists for potentiate NMDA receptor (NMDAR) currents, although mechanism by which this occurs still unclear. In study, we show vivo administration selective σ-1R (+)-SKF 10,047...
Short-term facilitation and depression have a profound influence on transmission at many glutamatergic synapses, particularly during trains of stimuli. A major component these processes is postsynaptic receptor desensitization. Both presynaptic mechanisms can contribute to synaptic efficacy, but it often difficult define their respective contributions. Blockers desensitization such as cyclothiazide (CTZ) be used, drugs nonspecific effects transmitter release, complicating attempts...
1. A hyperpolarization-activated non-specific cation current, I(h), was examined in bushy cell bodies and their giant presynaptic terminals (calyx of Held). Whole-cell patch clamp recordings were made using an vitro brain slice preparation the cochlear nucleus superior olivary complex. The aim to characterise I(h) identified synaptic terminals, examine modulation by cAMP test for modulatory effects activation on transmission. 2. Presynaptic activated hyperpolarizing voltage-steps, with...
P73 is important in drug-induced apoptosis some cancer cells, yet its role the regulation of chemosensitivity ovarian (OVCA) poorly understood. Furthermore, if and how deregulation p73-mediated confers resistance to cisplatin (CDDP) treatment unclear. Here we demonstrate that TAp73α over-expression enhanced CDDP-induced PARP cleavage both chemosensitive (OV2008 A2780s) their resistant counterparts (C13* A2780cp) another chemoresistant OVCA cells (Hey); contrast, effect ΔNp73α was variable....
Presynaptic group III metabotropic glutamate receptor (mGluR) activation by exogenous agonists (such as l ‐2‐amino‐4‐phosphonobutyrate ( ‐AP4)) potently inhibit transmitter release, but their autoreceptor function has been questioned because endogenous during high‐frequency stimulation appears to have little impact on synaptic amplitude. We resolve this ambiguity studying of mGluRs trains stimuli at the calyx Held. In vitro whole‐cell patch recordings were made from medial nucleus trapezoid...
The sigma-1 receptor (<i>σ</i>-1R) is an endoplasmic reticulum resident chaperone protein involved in a plethora of cellular functions, and whose disruption has been implicated wide range diseases. Genetic analysis revealed two <i>σ</i>-1R mutants neuromuscular disorders. A point mutation (E102Q) the ligand-binding domain results juvenile form amyotrophic lateral sclerosis (ALS16), 20 amino-acid deletion (Δ31–50) putative cytosolic leads to distal hereditary motor neuropathy. We investigated...
The activation of ligand-gated ion channels is thought to depend solely on the binding chemical neurotransmitters. In this study, we demonstrate that kainate (KA) ionotropic glutamate receptors (iGluRs) require not only neurotransmitter l -glutamate ( -Glu) but also external sodium and chloride ions for activation. Removal traps KA (KARs) in a novel inactive state binds -Glu with picomolar affinity. Moreover, occupancy KARs by precludes binding, demonstrating crosstalk between ligand-...
Activation of presynaptic receptors plays an important role in modulation transmission at many synapses, particularly during high-frequency trains stimulation. Adenosine-triphosphate (ATP) is coreleased with several neurotransmitters and acts sites to reduce transmitter release; such P2X occur inhibitory excitatory terminals the medial nucleus trapezoid body (MNTB). We have investigated mechanism purinergic repetitive stimulation calyx Held synapse. Suppression calyceal postsynaptic currents...
Kainate-selective ionotropic glutamate receptors (GluRs) require external Na<sup>+</sup> and Cl<sup>−</sup> as well the neurotransmitter l-glutamate for activation. Although, anions cations apparently coactivate kainate (KARs) in an identical manner, it has yet to be established how ions of opposite charge achieve this. An additional complication is that KARs are subject other forms cation modulation via extracellular acidification (i.e., protons) divalent ions. Consequently, species may...
Ischemic stroke is the second leading cause of death worldwide. Following an ischemic event, neuronal triggered by uncontrolled glutamate release to overactivation sensitive N-methyl-d-aspartate receptor (NMDAR). For gating, NMDARs require not only binding glutamate, but also glycine or a glycine-like compound as co-agonist. Low doses enhance NMDAR function, whereas high trigger glycine-induced internalization (GINI) in vitro. Here, we report that following vivo, GINI occurs and provides...
1 The single channel properties of P2X ATP receptors were investigated in outside-out patches from hippocampal granule cells brain slices 12-day-old rats. results demonstrate that functional are expressed and, combined with previously published information on the subunits hippocampus, suggest may be heteromers P2X4 and P2X6 or P2X1, P2X2, subunits. 2 Two distinct types openings observed. A flickery receptor was observed three a mean chord conductance 32 ± 6 pS, open time 1.0 0.3 ms burst...
Expression of Kv1.2 within Kv1.x potassium channel complexes is critical in maintaining appropriate neuronal excitability and determining the threshold for action potential firing. This attributed to interaction with a hitherto unidentified protein that confers bimodal activation gating, allowing neurons adapt repetitive trains stimulation protecting against hyperexcitability. One candidate sigma-1 receptor (Sig-1R), which regulates other members family; however, biophysical nature between...
Kainate-selective ionotropic glutamate receptors are unique among ligand-gated ion channels in their obligate requirement of external anions and cations for activation. Although it is established that the degree kainate receptor (KAR) activation shaped by chemical nature agonist molecule, possible complementary role ions has yet to be examined. Here we show but not regulate responsiveness a range full partial agonists acting on rat GluK2 receptors. This observation unexpected as previous...
The thalamus is a major relay and integration station in the central nervous system. While there large body of information on firing network properties neurons contained within sensory thalamic nuclei, less known about located midline which are thought to modulate arousal homeostasis. One nucleus that has been implicated mediating stress responses paraventricular (PVT). Like other neurons, these display two distinct modes, burst tonic. In contrast firing, little ionic mechanisms modulating...