A5030552116- Ion channel regulation and function
- Cardiac electrophysiology and arrhythmias
- Cellular transport and secretion
- Neuroscience and Neural Engineering
- Heart Rate Variability and Autonomic Control
- Receptor Mechanisms and Signaling
- Neuroscience and Neuropharmacology Research
- Nicotinic Acetylcholine Receptors Study
- Neurobiology and Insect Physiology Research
- Lysosomal Storage Disorders Research
- Neuroscience of respiration and sleep
- Lipid Membrane Structure and Behavior
- Calcium signaling and nucleotide metabolism
- Cell Image Analysis Techniques
- Cardiac pacing and defibrillation studies
- Mitochondrial Function and Pathology
- Pain Mechanisms and Treatments
- Advanced Fluorescence Microscopy Techniques
- Protein Kinase Regulation and GTPase Signaling
- Neural dynamics and brain function
- stochastic dynamics and bifurcation
- Ion Channels and Receptors
- Neurogenesis and neuroplasticity mechanisms
- Neuroendocrine regulation and behavior
- Advanced Electron Microscopy Techniques and Applications
University of Washington
2014-2025
Seattle University
2017-2023
Howard University
2023
Howard Hughes Medical Institute
2023
University of California, Davis
2017-2021
Center for Neurosciences
2018-2019
Universidad Popular Autónoma del Estado de Puebla
2019
Universidad Nacional Autónoma de México
2012-2014
Universidad Nacional de Colombia
2000-2010
Endoplasmic reticulum–plasma membrane (ER–PM) contact sites play an integral role in cellular processes such as excitation–contraction coupling and store-operated calcium entry (SOCE). Another ER–PM assembly is one tethered by the extended synaptotagmins (E-Syt). We have discovered that at steady state, E-Syt2 positions ER Sac1, lipid phosphatase, discrete junctions. Here, Sac1 participates phosphoinositide homeostasis limiting PM phosphatidylinositol 4-phosphate (PI(4)P), precursor of...
CaV-channel dependent activation of BK channels is critical for feedback control both calcium influx and cell excitability. Here we addressed the functional spatial interaction between CaV1.3 channels, unique CaV1 that activate at low voltages. We found when were co-expressed in same cell, started activating near −50 mV, ~30 mV more negative than high-voltage activated CaV2.2 channels. In addition, single-molecule localization microscopy revealed striking clusters surrounding forming a...
There is increasing evidence that the lysosome involved in pathogenesis of a variety neurodegenerative disorders. Thus, mechanisms link dysfunction to disruption neuronal homeostasis offer opportunities understand molecular underpinnings neurodegeneration and potentially identify specific therapeutic targets. Here, using monogenic disorder, NPC1 disease, we demonstrate reduced cholesterol efflux from lysosomes aberrantly modifies firing patterns. The mechanism linking alterations lysosomal...
Niemann-Pick type C1 (NPC1) protein is essential for the transport of externally derived cholesterol from lysosomes to other organelles. Deficiency NPC1 underlies progressive neurodegenerative disorder. Currently, there are no curative therapies this fatal disease. Given Ca2+ hypothesis neurodegeneration, which posits that altered dynamics contribute neuropathology, we tested if disease mutations in alter signaling and neuronal plasticity. We determine inhibition or potentiate store-operated...
Phosphoinositide membrane lipids are ubiquitous low-abundance signaling molecules. They direct many physiological processes that involve ion channels, identification, fusion of vesicles, and vesicular endocytosis. Pools these continually broken down refilled in living cells, the rates some reactions strongly accelerated by stimuli. Recent biophysical experiments described here measure model kinetics regulation lipid signals intact cells. Rapid on-line monitoring phosphoinositide metabolism...
Levels of nerve growth factor (NGF) are elevated in inflamed tissues. In sensory neurons, increases NGF augment neuronal sensitivity (sensitization) to noxious stimuli. Here, we hypothesized that also sensitizes sympathetic neurons proinflammatory We cultured superior cervical ganglion (SCG) from adult male Sprague Dawley rats with or without added and compared their responsiveness bradykinin, a peptide. The NGF-cultured exhibited significant depolarization, bursts action potentials, Ca 2+...
In neurons, loss of plasma membrane phosphatidylinositol 4,5-bisphosphate [PI(4,5)P 2 ] leads to a decrease in exocytosis and changes electrical excitability. Restoration PI(4,5)P levels after phospholipase C activation is therefore essential for return basal neuronal activity. However, the dynamics phosphoinositide metabolism have not been analyzed neurons. We measured dynamic , 4-phosphate, diacylglycerol, inositol 1,4,5-trisphosphate, Ca 2+ upon muscarinic stimulation sympathetic neurons...
Cholesterol and phosphoinositides (PI) are two critically important lipids that found in cellular membranes dysregulated many disorders. Therefore, uncovering molecular pathways connecting these essential may offer new therapeutic insights. We report loss of function lysosomal Niemann-Pick Type C1 (NPC1) cholesterol transporter, which leads to neurodegenerative NPC disease, initiates a signaling cascade alters the cholesterol/phosphatidylinositol 4-phosphate (PtdIns4P) countertransport cycle...
Calcium binding to BK channels lowers their activation threshold. Hence, are functionally coupled calcium-permeable channels. This functional coupling requires proximity of two different types Formation an ensemble at nanometer distances between and Ca V 1.3 exemplifies this unique organization. We investigated the mechanism underlying structural organization, testing hypothesis that assembly is formed before insertion plasma membrane. Our design used four approaches: 1) detect interaction...
A novel peptide, RsXXIVA, was isolated from the venom duct of Conus regularis, a worm-hunting species collected in Sea Cortez, México. Its primary structure determined by mass spectrometry and confirmed automated Edman degradation. This conotoxin contains 40 amino acids exhibits arrangement eight cysteine residues (C-C-C-C-CC-CC). Surprisingly, two loops peptide are highly identical to sequence ω-MVIIA. The total length disulfide pairing both peptides quite different, although most important...
A primary goal of molecular physiology is to understand how conformational changes proteins affect the function cells, tissues, and organisms. Here, we describe an imaging method for measuring voltage sensors endogenous ion channel within live tissue, without genetic modification. We synthesized GxTX-594, a variant peptidyl tarantula toxin guangxitoxin-1E, conjugated fluorophore optimal two-photon excitation through light-scattering tissue. term this tool EVAP (Endogenous Voltage-sensor...
Heart rate is accelerated to match physiological demands through the action of noradrenaline on cardiac pacemaker. Noradrenaline released from sympathetic terminals and activates β1-and β2-adrenergic receptors (ΑRs) located at plasma membrane pacemaker cells. L-type calcium channels are one main downstream targets potentiated by activation β-ARs. For this signaling occur, need be in close proximity β-ARs inside caveolae. Although it known that aging causes a slowdown reduction response cells...