A5069234700- Ion channel regulation and function
- Cardiac electrophysiology and arrhythmias
- Neuroscience and Neuropharmacology Research
- Cardiovascular Effects of Exercise
- Neuroscience and Neural Engineering
- Receptor Mechanisms and Signaling
- Mitochondrial Function and Pathology
- Cardiac Ischemia and Reperfusion
- Neural dynamics and brain function
- ATP Synthase and ATPases Research
- Transcranial Magnetic Stimulation Studies
- Liver Disease Diagnosis and Treatment
- Cardiac Fibrosis and Remodeling
- Diet and metabolism studies
- Cardiac Arrhythmias and Treatments
- Hydrogen's biological and therapeutic effects
- Advanced Fluorescence Microscopy Techniques
- Ionic liquids properties and applications
- Signaling Pathways in Disease
- Metabolism and Genetic Disorders
- Connexins and lens biology
- GABA and Rice Research
- Advanced Battery Technologies Research
- Hearing, Cochlea, Tinnitus, Genetics
- Cardiomyopathy and Myosin Studies
Rhode Island Hospital
2018-2024
Brown University
2018-2024
John Brown University
2023
Providence College
2019-2021
Harvard University
2009-2015
Boston Children's Hospital
2009-2015
Brandeis University
2015
The University of Texas Southwestern Medical Center
1995-1998
University of Florida Health Science Center
1998
Koltzov Institute of Developmental Biology
1994
Transcranial direct current stimulation (tDCS) is a method for modulating cortical excitability by weak constant electrical that applied through scalp electrodes. Although often described in terms of anodal or cathodal stimulation, depending on which electrode pole proximal to the region interest, it orientation neuronal structures relative (DC) vector determines effect tDCS. To investigate contribution neural pathway orientation, we studied DCS-mediated neuromodulation an vitro rat...
Excessive extracellular glutamate after traumatic brain injury (TBI) contributes to excitotoxic cell death and likely post-traumatic epilepsy. Glutamate transport is the only known mechanism of clearance, transporter 1 (GLT-1) major mammalian brain. We tested, by immunoblot, in rat lateral fluid percussion TBI model whether GLT-1 expression depressed cortex TBI, restored treatment with ceftriaxone, a well-tolerated β-lactam antibiotic previously shown enhance noninjured animals. then tested...
Glutamate released from synaptic vesicles mediates excitatory neurotransmission by stimulating glutamate receptors. transporters maintain low levels critical for this process, a role primarily attributed to astrocytes. Recently, vesicular release of unmyelinated axons in the rat corpus callosum has been shown elicit AMPA receptor-mediated currents glial progenitor cells. are only mechanism clearance, yet very little is known about normal development oligodendrocytes (OLs) or excitotoxic...
We have used capacitance measurements with a 1-microsecond voltage clamp technique to probe electrogenic ion-transporter interactions in giant excised membrane patches. The hydrophobic ion dipicrylamine was test model predictions for simple charge-moving reaction. and frequency dependencies of the apparent dipicrylamine-induced capacitance, monitored by 1-mV sinusoidal perturbations, correspond single charges moving across 76% field at rate 9500 s-1 0 mV. For cardiac Na,K pump, combined...
The QT interval is a recording of cardiac electrical activity. Previous genome-wide association studies identified genetic variants that modify the upstream LITAF (lipopolysaccharide-induced tumor necrosis factor-α factor), protein encoding regulator endosomal trafficking. However, it was not clear how might impact excitation. We investigated effect on voltage-gated sodium channel Nav1.5, which critical for depolarization. show overexpressed resulted in significant increase density...
BackgroundDiabetic (DM) inactivation of small conductance calcium-activated potassium (SK) channels contributes to coronary endothelial dysfunction. However, the mechanisms responsible for this down-regulation SK are poorly understood. Thus, we hypothesized that altered metabolic signaling in diabetes regulates and human microvascular function.MethodsHuman atrial tissue, arterioles artery cells (HCAECs) obtained from DM non-diabetic (ND) patients (n = 12/group) undergoing cardiac surgery...
Progressive tissue remodeling after myocardial infarction (MI) promotes cardiac arrhythmias. This process is well studied in young animals, but little known about pro-arrhythmic changes aged animals. Senescent cells accumulate with age and accelerate age-associated diseases. interfere function outcome post-MI age, studies have not been performed larger the mechanisms are unknown. Specifically, timecourse of senescence related inflammation fibrosis understood. Additionally, cellular systemic...
Sudden death in long-QT syndrome type 1 (LQT1), an inherited disease caused by loss-of-function mutations KCNQ1, is triggered early afterdepolarizations (EADs) that initiate polymorphic ventricular tachycardia (pVT). We investigated ionic mechanisms underlie pVT LQT1 using a transgenic rabbit model of LQT1.
To investigate coronary endothelial protection of a small-conductance calcium-activated potassium (SK) channel activator against period cardioplegic-hypoxia and reoxygenation (CP-H/R) injury in mice patients with diabetes (DM) those without (nondiabetic [ND]).Mouse small arteries/heart cells (MHECs) human arterial (HCAECs) were dissected from the harvested hearts (n = 16/group) discarded right atrial tissue samples DM 8/group). The SK current density MHECs was measured. vitro...
Long QT syndrome has been associated with sudden cardiac death likely caused by early afterdepolarizations (EADs) and polymorphic ventricular tachycardias (PVTs). Suppressing the late sodium current (INaL) may counterbalance reduced repolarization reserve in long prevent EADs PVTs. We tested effects of selective INaL blocker GS967 on PVT induction a transgenic rabbit model type 2 using intact heart optical mapping, cellular electrophysiology confocal Ca2+ imaging, computer modeling....
During long-term potentiation (LTP) of excitatory synapses, Ca(2+)/calmodulin-dependent protein kinase II (CaMKII) is activated by Ca(2+) influx through NMDA receptors that potentiate AMPA receptor currents insertion additional GluR1-containing at the synapse and increasing channel conductance, as well stimulating structural changes. CaMKII also involved in maintenance LTP contributes to behavioral sensitization cocaine or amphetamine. Recent studies show transient expression catalytically...
Genome-wide association studies have reported a correlation between SNP of the RING finger E3 ubiquitin protein ligase rififylin (RFFL) and QT interval variability in humans (Newton-Cheh et al., 2009). Previously, we shown that RFFL downregulates expression function human-like ether-a-go-go-related gene potassium channel corresponding rapidly activating delayed rectifier current (I
Lithium's therapeutic specificity for the treatment of bipolar disorder may be attributable in part to an ability target sites where there are high levels synaptic activity. We show that glutamate receptors expressed oocytes highly permeable lithium. Mathematical simulations Li+ diffusion mature dendritic spines suggest presence 1 mM extracellular lithium one current can increase concentration spine head by 4 with a decay time constant about 15-20 ms. Two or more spikes will produce...
Background: The turnover of cardiac ion channels underlying action potential duration is regulated by ubiquitination. Genome-wide association studies QT interval identified several single-nucleotide polymorphisms located in or near genes involved protein A genetic variant upstream LITAF (lipopolysaccharide-induced tumor necrosis factor) gene prompted us to determine its role modulating excitation. Methods: Optical mapping was performed zebrafish hearts Ca 2+ transients. Live-cell confocal...
Cardiac arrhythmias significantly contribute to cardiovascular morbidity and mortality. The rabbit heart serves as an accepted model system for studying cardiac cell excitation arrhythmogenicity. Accordingly, primary cultures of adult ventricular cardiomyocytes serve a preferable study molecular mechanisms human excitation. However, the use is often regarded excessively costly. Therefore, we developed characterized novel low-cost cardiomyocyte model, namely, 3-week-old (3wRbCMs). Ventricular...
Abstract Glutamate is the major excitatory neurotransmitter of central nervous system and toxic to neurons even at low concentrations. GLT1, rodent analog human EAAT2, primarily responsible for glutamate clearance in cerebrum. GLT1 was thought be expressed exclusively astrocytes mature brain. Recently, however, GLT1a demonstrated axon terminals where synaptic concentration rises above 1 m during transmission. function with accurate control both intracellular extracellular solutions mimicking...
Glutamate is the major excitatory neurotransmitter, but prolonged exposure even at micromolar concentrations causes neuronal death. Extracellular glutamate maintained nanomolar level by transporters, which, however, may reverse transport and release glutamate. If when occurs depends on stoichiometry (GTS). Previously we found that in presence of chloride, coupled GLT-1 transporter current its relationship to radiolabeled flux significantly decreased extracellular concentration increased...