A5064817888- Ion channel regulation and function
- Neuroscience and Neuropharmacology Research
- Cellular transport and secretion
- Cardiac electrophysiology and arrhythmias
- Multiple Sclerosis Research Studies
- Lipid Membrane Structure and Behavior
- Peripheral Neuropathies and Disorders
- Pain Mechanisms and Treatments
- Photoacoustic and Ultrasonic Imaging
- Optical Imaging and Spectroscopy Techniques
- Nicotinic Acetylcholine Receptors Study
- Calcium signaling and nucleotide metabolism
- Erythrocyte Function and Pathophysiology
- Neuroscience and Neural Engineering
- Autoimmune and Inflammatory Disorders Research
- Receptor Mechanisms and Signaling
- Vaccine Coverage and Hesitancy
- Connexins and lens biology
- Spine and Intervertebral Disc Pathology
- Traumatic Brain Injury and Neurovascular Disturbances
- Pain Management and Opioid Use
- Gait Recognition and Analysis
- Migraine and Headache Studies
- COVID-19 Clinical Research Studies
- Smoking Behavior and Cessation
University of Calgary
2009-2023
Spinal Cord Injury Alberta
2023
Institut de Génomique Fonctionnelle
2012
Laboratoire de Mathématiques d'Orsay
2012
Inserm
2012
Université de Montpellier
2012
Health Sciences Centre
2003
The direct modulation of N-type calcium channels by G protein βγ subunits is considered a key factor in the regulation neurotransmission. Some molecular determinants that govern binding interaction and Gβγ have recently been identified (see, <i>i.e.</i>, Zamponi, G. W., Bourinet, E., Nelson, D., Nargeot, J., Snutch, T. P. (1997)<i>Nature</i> 385, 442–446); however, little known about cellular mechanisms modulate this interaction. Here we report presynaptic vesicle release complex, syntaxin...
Accurate calcium signaling requires spatial and temporal coordination of voltage-gated channels (VGCCs) a variety signal transduction proteins. Accordingly, regulation L-type VGCCs involves the assembly complexes that include channel subunits, protein kinase A (PKA), anchoring proteins (AKAPs), β2-adrenergic receptors, although molecular details underlying these interactions remain enigmatic. We show here, by combining extracellular epitope splicing into pore-forming subunit immunoassays...
We have reported recently that syntaxin 1A mediates two effects on N-type channels transiently expressed in tsA-201 cells: a hyperpolarizing shift the steady-state inactivation curve as well tonic inhibition of channel by G-protein βγ subunits (Jarvis et al., 2000). Here we examined some molecular determinants and factors modulate action calcium channels. With additional coexpression SNAP25, 1A-induced modulation became reduced magnitude ∼50% but nonetheless remained significantly higher...
We recently described domains II and III as important determinants of fast, voltage-dependent inactivation R-type calcium channels (Spaetgens, R. L., Zamponi, G. W. (1999) J. Biol. Chem. 274, 22428–22438). Here we examine in greater detail the structural using a series chimeras comprising various regions wild type α1C α1Ecalcium channels. Substitution S6 and/or segments α1E into backbone resulted rapid rates that closely approximated those However, neither individual or combined substitution...
We report here that unlike what was suggested for many vertebrate neurons, synaptic transmission in <i>Lymnaea stagnalis</i> occurs independent of a physical interaction between presynaptic calcium channels and functional complement SNARE proteins. Instead, <i>Lymnaea</i>requires the expression C-terminal splice variant the<i>Lymnaea</i> homolog to mammalian N- P/Q-type channels. show alternately spliced region physically interacts with scaffolding proteins Mint1 CASK, is abolished following...
We have previously reported that syntaxin 1A, a component of the presynaptic SNARE complex, directly modulates N-type calcium channel gating in addition to promoting tonic G-protein inhibition channels, whereas 1B affects but does not support modulation (Jarvis, S. E., and Zamponi, G. W. (2001) J. Neurosci. 21, 2939-2948). Here, we investigated molecular determinants govern action 1 isoforms on function. In vitro evidence shows both physically interact with beta subunit synaptic protein...
The physical interaction between the presynaptic vesicle release complex and large cytoplasmic region linking domains II III of N-type (Ca(v)2.2) calcium channel alpha(1)B subunits is considered to be fundamental importance for efficient neurotransmission. By PCR analysis human brain cDNA libraries IMR32 cell mRNA, we have isolated novel variants, termed Ca(v)2.2-Delta1 Delta2, which lack parts domain II-III linker region, including synaptic protein site. They appear widely expressed across...
Using transient calcium phosphate transfection into the human embryonic kidney tsa-201 cell line and subsequent whole-cell patch-clamp protocols, we examined tonic modulation of cloned N- P/Q-type channels by five different G protein beta subunits via strong depolarizing voltage prepulses. For channels, magnitude inhibition was dependent on Gbeta subtype co-expressed. Both absolute relative magnitudes subunit-induced differed from those observed with N-type channel. each channel subtype,...
The modulation of N-type calcium current by protein kinases and G-proteins is a factor in the fine tuning neurotransmitter release. We have previously shown that phosphorylation threonine 422 α1B channel domain I-II linker region resulted dramatic reduction somatostatin receptor-mediated G-protein inhibition channels consequently serves as an integration center for cross-talk between kinase C (PKC) (Hamid, J., Nelson, D., Spaetgens, R., Dubel, S. Snutch, T. P., Zamponi, G. W. (1999) J. Biol....
N-type Ca(2+) channels are modulated by a variety of G-protein-coupled pathways. Some pathways produce transient, voltage-dependent (VD) inhibition N channel function and involve direct binding G-protein subunits; others require the activation intermediate enzymes longer-lasting, voltage-independent (VI) form inhibition. The ratio VD:VI differs significantly among cell types, suggesting that two forms play unique physiological roles in nervous system. In this study, we explored mechanisms...
Disease modifying therapies (DMTs) reduce the frequency of relapses and accumulation disability in multiple sclerosis (MS). Long-term persistence with treatment is important to optimize benefit. This long-term, cohort study was conducted at Calgary MS Clinic. All consenting adults relapsing-remitting who started either glatiramer acetate (GA) or interferon-β 1a/1b (IFN-β) between January 1st, 1996 July 2011 were included. Follow-up continued February 2014. Time-to-discontinuation initial...
The etiology of fatigability from whole body exercise was examined for the first time to accurately elucidate relationship between fatigue and in multiple sclerosis (MS). Compromised corticospinal responsiveness predicted severity, providing a novel, objective indicator MS. Although impaired corticomotor transmission did not aggravate muscle activation this group people with (PwMS) lower disability, heightened seen contribute perceptions PwMS.
It is widely believed that the selectivity of voltage-dependent calcium channels mainly controlled by amino acid residues contained within four p-loop motifs forming pore channel. An examination sequences high voltage-activated reveals their domain III S5–H5 regions contain a highly conserved motif with homology to known EF hand binding proteins, hinting this region may contribute channel permeation. To test hypothesis, we used site-directed mutagenesis replace three negatively charged in...
Complexes of specific presynaptic proteins have been hypothesized to drive or catalyze the membrane fusion steps exocytosis. Here we use a stage-specific preparation test roles SNAREs, synaptotagmin, and SNARE-binding in mechanism Ca2+-triggered fusion. Excess exogenous proteins, sufficient block SNARE interactions, did not inhibit either Ca2+ sensitivity, extent, kinetics In contrast, despite limited effect on synaptotagmin densities, treatments with high doses chymotrypsin markedly...
Cysteine string proteins (CSPs) are secretory vesicle chaperones that important for neurotransmitter release. We have previously reported an interaction of CSP with both heterotrimeric GTP-binding (G proteins)and N-type calcium channels results in a tonic G protein inhibition the channels. In this report we directly demonstrate two separate regions associate proteins. The N-terminal binding site CSP, which includes J domain, binds Gα subunits but not Gαβ whereas C terminal associates either...
Annexin II tetramer (AIIt) is a Ca2+-dependent, phosphatidylserine-binding, and F-actin-bundling phosphoprotein which localized to both the extracellular cytoplasmic surfaces of plasma membrane. The composed two p36 heavy chains p11 light chains. We have produced prokaryotic cDNA expression constructs for p11. Both proteins were expressed in large amounts Escherichia coli upon induction with IPTG. Electrospray ionization mass spectrometry amino acid sequence analysis purified recombinant...
Multiple sclerosis (MS) is a degenerative disease of the central nervous system (CNS) characterized by inflammation, demyelination, and axonal damage. It has been hypothesized that hypoxia plays role in pathogenesis MS. This study was undertaken to investigate reproducibility non-invasively measured cortical microvascular hemoglobin oxygenation (St O2 ) using frequency domain near-infrared spectroscopy (fdNIRS), its temporal pattern people with MS (pwMS), relationship neurocognitive function...