A5020954929- Neuroscience and Neuropharmacology Research
- Ion channel regulation and function
- Cardiac electrophysiology and arrhythmias
- Photoreceptor and optogenetics research
- Neuroscience and Neural Engineering
- Anesthesia and Neurotoxicity Research
- Macrophage Migration Inhibitory Factor
- Monoclonal and Polyclonal Antibodies Research
- Electrostatic Discharge in Electronics
- Ubiquitin and proteasome pathways
- Receptor Mechanisms and Signaling
- Integrated Circuits and Semiconductor Failure Analysis
- Infant Nutrition and Health
- Retinal Development and Disorders
- Cardiac Arrhythmias and Treatments
- Advanced Memory and Neural Computing
- Glycosylation and Glycoproteins Research
- Photochromic and Fluorescence Chemistry
- Cellular transport and secretion
- VLSI and Analog Circuit Testing
Cornell University
2011-2015
University of Virginia
2002-2008
University of Virginia Health System
2007
Cold Spring Harbor Laboratory
2005
Max Planck Institute for Medical Research
2005
Synaptic trafficking of AMPA-Rs, controlled by small GTPase Ras signaling, plays a key role in synaptic plasticity. However, how signals AMPA-R is unknown. Here we show that low levels activity stimulate extracellular signal-regulated kinase (MEK)–p42/44 MAPK (extracellular [ERK]) whereas high additional Pi3 (Pi3K)–protein B (PKB) each accounting for ∼50% the potentiation during long-term (LTP). Spontaneous neural stimulates Ras–MEK–ERK pathway drives GluR2L into synapses. In presence...
T-type Ca 2+ channels (T-channels) are involved in the control of neuronal excitability and their gating can be modulated by a variety redox agents. Ascorbate is an endogenous agent that function as both anti- pro-oxidant. Here, we show ascorbate selectively inhibits native v 3.2 T-channels peripheral central neurons, well recombinant heterologously expressed human embryonic kidney 293 cells, initiating metal-catalyzed oxidation specific, metal-binding histidine residue domain 1 channel. Our...
Identifying presynaptic mechanisms of general anesthetics is critical to understanding their effects on synaptic transmission. We show that the volatile anesthetic isoflurane inhibits vesicle (SV) exocytosis at nerve terminals in dissociated rat hippocampal neurons through inhibition Ca(2+) influx without significantly altering sensitivity SV exocytosis. A clinically relevant concentration (0.7 mM) inhibited changes [Ca(2+)]i driven by single action potentials (APs) 25 ± 3%, which turn led...
The intracellular loops that interlink the four transmembrane domains of Ca(2+)- and Na(+)-channels (Ca(v), Na(v)) have critical roles in numerous forms channel regulation. In particular, loop joins repeats I II (I-II loop) high voltage-activated (HVA) Ca(2+) channels possesses binding site for Ca(v)beta subunits plays significant function, including trafficking alpha(1) HVA to plasma membrane gating. Although there is considerable divergence primary sequence I-II Ca(v)1/Ca(v)2 Ca(v)3...
Mutations in the I-II loop of Cav3.2 channels were discovered patients with childhood absence epilepsy. All these mutations increased surface expression channel, whereas some mutations, and particular C456S, altered biophysical properties channels. Deletions around C456S found to produce that opened at even more negative potentials than control, suggesting presence a gating brake normally prevents channel opening. The goal present study was identify minimal sequence this provide insights...
Molecular diversity of T‐type/Ca v 3 Ca 2+ channels is created by expression three genes and alternative splicing those genes. Prompted the important role I–II linker in gating surface channels, we describe here properties a novel variant that partially deletes this loop. The abundantly expressed rat brain, even exceeding transcripts with complete exon 8. Electrophysiological analysis Δ8b revealed enhanced current density compared to 3.1a, but similar gating. Luminometry experiments an...
The Ca(v)beta subunits of high voltage-activated Ca(2+) channels control the trafficking and biophysical properties alpha(1) subunit. Ca(v)beta-alpha(1) interaction site has been mapped by crystallographic studies. Nevertheless, how this leads to channel regulation not determined. One hypothesis is that betas regulate gating modulating movements IS6. A key requirement for direct-coupling model linker connecting IS6 alpha-interaction domain (AID) be a rigid structure.The present study tests...
Volatile anesthetics have poorly understood mechanisms of action, despite their wide usage in medicine. Current knowledge the molecular and cellular anesthetic action is insufficient to explain amnesia, unconsciousness or immobilization, principal features general anesthesia. The volatile isoflurane alters synaptic transmission by blocking ionotropic glutamate receptors postsynaptically and/or enhancing fast inhibitory tonic currents mediated GABA A receptors. However, dopaminergic neurons,...