- Neuroscience of respiration and sleep
- Neuroscience and Neuropharmacology Research
- Heart Rate Variability and Autonomic Control
- Pain Mechanisms and Treatments
- Advanced Glycation End Products research
- Ion channel regulation and function
- Nitric Oxide and Endothelin Effects
- Cystic Fibrosis Research Advances
- Nicotinic Acetylcholine Receptors Study
- Adenosine and Purinergic Signaling
- Inhalation and Respiratory Drug Delivery
- Alzheimer's disease research and treatments
- Receptor Mechanisms and Signaling
- Tracheal and airway disorders
- Neonatal and fetal brain pathology
- Parkinson's Disease Mechanisms and Treatments
- Biochemical effects in animals
- High Altitude and Hypoxia
- Respiratory viral infections research
- Neonatal Respiratory Health Research
- Vagus Nerve Stimulation Research
- Neuroendocrine regulation and behavior
- Prenatal Substance Exposure Effects
- Advanced Chemical Sensor Technologies
- Neurological Disorders and Treatments
Respiratory Clinical Trials
2024
Czech Academy of Sciences, Institute of Physiology
2024
University of Saskatchewan
2012-2022
Saskatoon Medical Imaging
2020
Saskatchewan Health
2017
Hospital for Sick Children
2013
McGill University
2006-2010
McMaster University
2003-2007
Pulmonary ionocytes are a newly discovered airway epithelial cell type proposed to be major contributor cystic fibrosis (CF) lung disease based on observations they express the transmembrane conductance regulator (CFTR) anion channel at higher level than any other in epithelia. Moreover, genetically manipulated experimental models that lack develop NaCl transport abnormalities and surface liquid (ASL) dehydration consistent with CF. However, no direct evidence indicates engage or contribute...
Neuronal nicotinic acetylcholine receptors (nAChRs), ligand-gated ion channels implicated in a variety of cognitive, motor, and sensory behaviours, are targeted to compartments rich mitochondria, particularly postsynaptic domains presynaptic terminals, exposing these reactive oxygen species (ROS) generated by oxidative phosphorylation. In addition, can become exposed ROS during the progression certain neurodegenerative diseases. Because known modify several membrane proteins, including some...
In mammals, ventilation is peripherally controlled by the carotid body (CB), which receives afferent innervation from petrosal ganglion and efferent neurons located along glossopharyngeal nerve (GPN). GPN give rise to “efferent inhibitory” pathway via a plexus of neuronal nitric oxide (NO) synthase-positive fibers, believed be responsible for CB chemoreceptor inhibition NO release. Although elevated during natural stimulation hypoxia, underlying mechanisms are unclear. We hypothesized that...
Graphical Abstract figure legend HCN channels play an evolutionarily conserved pacemaker role in renal pelvic smooth muscle (RPSM) of lower and higher order mammals. The function hyperpolarization-activated cation (HCN) pacemakers remains controversial. Renal trigger contractions that expel waste from the kidney, have been localized to these tissues. To date, however, mechanisms underlying RPSM activity remain elusive. was investigated both (top left) (bottom mammalian models, which exhibit...
Cystic fibrosis (CF) is an autosomal recessive genetic disorder caused by mutations in the gene encoding for anion channel cystic transmembrane conductance regulator (CFTR). Several organs are affected CF, but most of morbidity and mortality comes from lung disease. Recent data show that initial consequence CFTR mutation failure to eradicate bacteria before development inflammation airway remodeling. Bacterial clearance depends on a layer surface liquid (ASL) consisting both mucus traps,...
Diabetes mellitus is associated with sensory abnormalities, including exacerbated responses to painful (hyperalgesia) or non-painful (allodynia) stimuli. These abnormalities are symptoms of diabetic peripheral neuropathy (DPN), which the most common complication that affects approximately 50% patients. Yet, underlying mechanisms linking hyperglycemia and DPN remain poorly understood. The transient receptor potential vanilloid 1 (TRPV1) channel plays a central role in such shows elevated...
Abstract Cystic fibrosis is caused by mutations in the gene encoding cystic transmembrane conductance regulator (CFTR) channel, which can result chronic lung disease. The sequence of events leading to disease not fully understood but recent data show that critical pathogenic event loss ability clear bacteria due abnormal airway surface liquid secretion (ASL). However, whether inhalation triggers ASL and this has never been tested. Here we show, using a novel synchrotron-based vivo imaging...
Modulation of K+ channels by hypoxia is a common O2-sensing mechanism in specialised cells. More recently, acid-sensitive TASK-like background channels, which play key role setting the resting membrane potential, have been implicated certain cell types. Here, we report novel O2 sensitivity mediated weakly pH-sensitive conductance nitric oxide synthase (NOS)-positive neurones glossopharyngeal nerve (GPN). This was insensitive to 30 mM TEA, 5 4-aminopyridine (4-AP) and 200 microM Cd2+, but...
Abstract Background NMDA receptors are ligand-gated ion channels with essential roles in glutamatergic synaptic transmission and plasticity the CNS. As co-receptors for glutamate glycine, gating of receptor/channel pore requires agonist binding to glycine sites, as well on ligand-binding domains receptor. In addition channel gating, has been found prime internalization upon subsequent stimulation sites. Results Here we address key issue identifying molecular determinants glycine-binding...
Abstract Autonomic dysfunction is a serious complication of diabetes and can lead to cardiovascular abnormalities premature death. It was recently proposed that autonomic triggered by oxidation‐mediated inactivation neuronal nicotinic acetylcholine receptors (nAChRs), impairing synaptic transmission in sympathetic ganglia resulting failure. We investigated whether the receptor for advanced glycation end products (RAGE) its role generation reactive oxygen species (ROS) could be contributing...
Abstract Thoracic dorsal root ganglia (tDRG) contribute to fluid secretion in the upper airways. Inflammation potentiates DRG responses, but mechanisms remain under investigation. The receptor for advanced glycation end-products (RAGE) underlies potentiation of responses pain pathologies; however, its role other sensory modalities is less understood. We hypothesize that RAGE contributes electrophysiological and biochemical changes tDRGs during inflammation. used tracheas from wild types...
The mammalian carotid body (CB) is a peripheral chemosensory organ that controls ventilation and innervated by both afferent efferent nerve fibres. pathway stimulated chemoexcitants, such as hypoxia, hypercapnia acidosis. causes inhibition of the sensory discharge via release NO originates mainly from neuronal nitric oxide synthase (nNOS)-positive autonomic neurones within glossopharyngeal (GPN). Recent studies in rat indicate these inhibitory GPN their processes express purinergic P2X...
A controversial hypothesis pertaining to cystic fibrosis (CF) lung disease is that the CF transmembrane conductance regulator (CFTR) channel fails inhibit epithelial Na+ (ENaC), yielding increased reabsorption and airway dehydration. We use a non-invasive self-referencing Na+-selective microelectrode technique measure transport across individual folds of distal surface epithelium preparations from CFTR−/− wild-type (WT) swine. show that, under unstimulated control conditions, WT epithelia...