A5065957388- Ion channel regulation and function
- Neuroscience and Neuropharmacology Research
- Nicotinic Acetylcholine Receptors Study
- Cardiac electrophysiology and arrhythmias
- Neuroscience and Neural Engineering
- Receptor Mechanisms and Signaling
- Heart Rate Variability and Autonomic Control
- Pain Mechanisms and Treatments
- Insect and Pesticide Research
- Ion Channels and Receptors
- Neurobiology and Insect Physiology Research
- Neuropeptides and Animal Physiology
- Lipid Membrane Structure and Behavior
- Neural dynamics and brain function
- Ion Transport and Channel Regulation
- Analytical Chemistry and Sensors
- Photoreceptor and optogenetics research
- Neuroscience of respiration and sleep
- Connexins and lens biology
- Cholinesterase and Neurodegenerative Diseases
- Cardiomyopathy and Myosin Studies
- Synthesis and pharmacology of benzodiazepine derivatives
- Calcium signaling and nucleotide metabolism
- Transcranial Magnetic Stimulation Studies
- Plant-based Medicinal Research
A.T. Still University
2015-2024
Tulane University
2000-2015
University of Health Sciences
2013-2015
University of New Orleans
2015
University of Health Science
2015
University of Health Sciences Antigua
2013
Penn State Milton S. Hershey Medical Center
2006-2011
Pennsylvania State University
2007-2010
Jeonbuk National University
1999
Case Western Reserve University
1990-1994
Significance This study addresses the need to phase out opioids as major analgesic drugs for moderate severe chronic pain. We establish that a highly selective and potent inhibitor of α9α10 nicotinic acetylcholine receptor (nAChR) subtype prevents expression chemotherapy-induced neuropathic Thus, antagonists nAChR are potential leads nonopioid drug development. The effects inhibitors receptor, together with genetic studies, suggest key role in an intercellular signaling network can be...
Significance The α9α10 nicotinic AChR (nAChR) subtype is a recently identified target for the development of breast cancer chemotherapeutics and analgesics, particularly to treat neuropathic pain. Structure/function analyses antagonists this are therefore essential specific therapeutic compounds. Conus genus rich source pharmacologically active peptides, we report here that αO-conotoxin GeXIVA potent selective antagonist nAChR subtype. displays unique structural properties among other...
Action potential-evoked neurotransmitter release is impaired in knock-out neurons lacking synaptic cell-adhesion molecules α-neurexins (αNrxns), the extracellularly longer variants of three vertebrate Nrxn genes. Ca2+ influx through presynaptic high-voltage gated calcium channels like ubiquitous P/Q-type (CaV2.1) triggers fusion-ready vesicles at many boutons. α2δ Auxiliary subunits regulate trafficking and kinetic properties CaV2.1 pore-forming but it has remained unclear if this involves...
Timothy syndrome (TS) is a multiorgan dysfunction caused by Gly to Arg substitution at position 406 (G406R) of the human CaV1.2 (L-type) channel. The TS phenotype includes severe arrhythmias that are thought be triggered impaired open-state voltage-dependent inactivation (OSvdI). effect mutation on other L-channel gating mechanisms has yet investigated. We compared kinetic properties exogenously expressed (HEK293 cells) rabbit cardiac L-channels with (G436R; corresponding in clone) and...
Structural and functional studies of small, disulfide-rich peptides depend on their efficient chemical synthesis folding. A large group derived from animals plants contains the Cys pattern C-C-CC-C-C that forms inhibitory cystine knot (ICK) or knottin motif. Here we report effect site-specific incorporation pairs selenocysteine residues oxidative folding activity omega-conotoxin GVIA, a well-characterized ICK-motif peptidic antagonist voltage-gated calcium channels. Three selenoconotoxin...
1. Whole‐cell calcium currents of bullfrog sympathetic neurones were partially inhibited by noradrenaline (NA), chicken‐II‐luteinizing hormone‐releasing hormone (LHRH), muscarine, ATP, substance P, or intracellular dialysis with guanosine 5'‐O‐(3‐thiotriphosphate)(GTP‐gamma‐S) aluminium fluoride. These agents had similar effects on the activation kinetics current. 2. The amplitude LHRH effect varied from cell to cell. This did not correlate size time whole‐cell dialysis. 3. response...
Human ether-a-go-go-related gene (HERG) potassium channel acts as a delayed rectifier in cardiac myocytes and is an important target for both pro- antiarrhythmic drugs. Many drugs have been pulled from the market unintended HERG block causing arrhythmias. Conversely, recent evidence has shown that plays role cell proliferation overexpressed multiple tumor lines primary cells, which makes attractive cancer treatment. Therefore, drug can but does not induce arrhythmias would great therapeutic...
L-type calcium channels (Ca((V))1.2) play an important role in cardiac contraction. Roscovitine, a cyclin-dependent kinase inhibitor and promising anticancer drug, has been shown to affect Ca((V))1.2 by inhibiting current amplitude slowing activation. This research investigates the mechanism which roscovitine inhibits channels.Ca((V))1.2 were transfected into HEK 293 cells, using phosphate precipitation method, currents measured whole-cell patch clamp technique.Roscovitine slows activation...
Propofol is commonly used to induce anesthesia but has been associated with some negative cardiovascular side effects, including inotropy, hypotension, and bradycardia. This study investigated the effect of propofol on L-type calcium current in acutely isolated human atrial myocytes better understand mechanism these effects. After informed consent was obtained, appendage obtained from patients undergoing open-heart surgery who required cardiopulmonary bypass. Atrial were using enzymatic...
1. Noradrenaline (NA) slows the activation kinetics of N‐type calcium channels, via G proteins. It has been suggested that proteins act by binding directly to channels. If slow reflect and unbinding proteins, rates should depend on concentration activated protein. 2. We used different concentrations NA, increasing durations intracellular dialysis with GTP‐gamma‐S, vary 3. At depolarized potentials (‐20 or ‐10 mV), showed no detectable dependence. This analysis required correction for effects...
Sensory neurons in the dorsal root ganglia (DRG) express a subset of voltage dependent sodium channels (NaV) including NaV1.1, 1.6, 1.7, 1.8 and 1.9. Previous work supported preferential localization NaV1.8 to small-medium diameter, nociceptive afferent neurons. However, we recently published evidence that was dominant NaV channel expressed somas small, medium large diameter muscle neurons, which is consistent with other reports. Here, extend those results show expression not correlated...
Whole-cell recordings have been used to extensively characterize the voltage-dependent inhibition of N-type calcium current induced by various neurotransmitters. Results from these studies yielded several predictions on effect N-channel gating, namely delayed channel opening and inhibition-induced reluctant openings. Previous single observed but failed find However, strong depolarizations may be necessary see openings, this was not tested. We examined gating at voltages depolarized those...
Most of the whole-cell calcium current frog sympathetic neurons is an N-type current, blocked by ω-conotoxin GVIA (ωCGVIA). Thus, these cells should be excellent system to study properties single channels. However, a channel that active near −10 mV in isotonic Ba 2+ , originally identified as “N-type,” corresponds more closely ωCGVIA-resistant component observed 100 m . That conclusion would imply true single-channel correlate macroscopic N-current remains neurons. I report here recordings...
1. Neurotransmitters (noradrenaline, NA; chicken II luteinizing hormone‐releasing hormone, LHRH) and activators of G proteins (GTP‐gamma‐S AlF3) partially inhibit calcium current in bullfrog sympathetic neruones. Activation the remaining is slowed shifted to more positive voltages. 2. The N‐type appears be type modulated, since approximately 90% peak blocked by omega‐conotoxin (omega CgTx) modulation not affected nisoldipine. 3. Calcium at relatively negative voltages (‐30 ‐50 mV) resistant...