A5075756207- Ion channel regulation and function
- Neuroscience and Neuropharmacology Research
- Alzheimer's disease research and treatments
- Neuroinflammation and Neurodegeneration Mechanisms
- Ion Transport and Channel Regulation
- Ion Channels and Receptors
- Barrier Structure and Function Studies
- Cardiac electrophysiology and arrhythmias
- Intensive Care Unit Cognitive Disorders
- S100 Proteins and Annexins
- Nitric Oxide and Endothelin Effects
- Dementia and Cognitive Impairment Research
- Receptor Mechanisms and Signaling
- Nosocomial Infections in ICU
- Amyloidosis: Diagnosis, Treatment, Outcomes
- Caveolin-1 and cellular processes
- Neonatal and fetal brain pathology
- Pancreatitis Pathology and Treatment
- Angiogenesis and VEGF in Cancer
- Neuroscience of respiration and sleep
- Cardiovascular, Neuropeptides, and Oxidative Stress Research
- Temporomandibular Joint Disorders
- Cancer, Stress, Anesthesia, and Immune Response
- Machine Learning in Bioinformatics
- Molecular Sensors and Ion Detection
University of South Alabama
2015-2024
Loma Linda University
1999-2015
Garvan Institute of Medical Research
2015
University of Southern Denmark
2013
Fundacion Agencia Aragonesa para la Investigacion y el Desarrollo
2013
Instituto de Investigación Sanitaria Aragón
2013
Alcon (United States)
2012
Vollum Institute
2008-2012
Oregon Health & Science University
2008-2012
Pseudomonas aeruginosa pneumonia elicits endothelial cell release of cytotoxic amyloids that can be recovered from the bronchoalveolar lavage and cerebrospinal fluids critically ill patients. Introduction these into lateral ventricle impairs learning memory in mice. However, it is unclear whether lung origin (1) are neurotropic, (2) cause structural remodeling hippocampal dendrites. Thus, we used electrophysiological studies brain slices analysis post-mortem tissues obtained animals exposed...
Intermediate and small conductance KCa channels IK1 (KCa3.1) SK3 (KCa2.3) are primary targets of endothelial Ca(2+) signals in the arterial vasculature, their ablation results increased tone hypertension. Activation by local transients from internal stores or plasma membrane promotes hyperpolarization vasodilation. Here, we assess arteries genetically altered knockout mice (IK1(-/-)) to determine whether exert a positive feedback influence on dynamics.Using confocal imaging custom data...
Abstract We investigated the temporal and spatial expression of SK2 in developing mouse hippocampus using molecular biochemical techniques, quantitative immunogold electron microscopy, electrophysiology. The mRNA encoding was expressed adult hippocampus. Western blotting immunohistochemistry showed that protein increased with age. This accompanied by a shift subcellular localization. Early development (P5), predominantly localized to endoplasmic reticulum pyramidal cell layer. But P30 almost...
Our previous work has shown that the increased lung endothelial permeability response to 14,15-epoxyeicosatrienoic acid (14,15-EET) in rat requires Ca(2+) entry via vanilloid type-4 transient receptor potential (TRPV4) channels. Recent studies suggest activation of TRPV4 channels systemic vascular endothelium prolongs agonist-induced hyperpolarization and amplifies by activating Ca(2+)-activated K(+) (KCa) channels, resulting vessel relaxation. Activation KCa thus increase electrochemical...
Abstract Pneumonia causes short‐ and long‐term cognitive dysfunction in a high proportion of patients, although the mechanism(s) responsible for this effect are unknown. Here, we tested hypothesis that pneumonia‐elicited cytotoxic amyloid tau variants: (1) present circulation during infection; (2) lead to impairment potentiation; and, (3) inhibit potentiation dependent upon tau. Cytotoxic species were recovered from blood hippocampus following pneumonia, they extracorporeal membrane...
Patients who recover from nosocomial pneumonia oftentimes exhibit long-lasting cognitive impairment comparable with what is observed in Alzheimer's disease patients. We previously hypothesized that the lung endothelium contributes to infection-related neurocognitive dysfunction, because bacteria-exposed endothelial cells release a form(s) of cytotoxic tau sufficient impair long-term potentiation hippocampus. However, full-length and isoform(s) have yet be resolved it remains unclear whether...
Small conductance Ca 2+ -activated K + type 2 (SK2) channels are expressed in the postsynaptic density of CA1 neurons where they activated by synaptically evoked influx to limit size EPSPs and spine transients. At Schaffer collateral synapses, induction long-term potentiation (LTP) increases α-amino-3-hydroxyl-5-methyl-4-isoxazole-propionate receptor (AMPAR)-mediated contribution synaptic transmission decreases SK2 channel through protein kinase A-dependent endocytosis. Using a combination...
Activation of vascular endothelial small- (KCa2.3, SK3) or intermediate- (KCa3.1, IK1) conductance Ca(2+)-activated potassium channels induces vasorelaxation via an endothelium-derived hyperpolarization (EDH) pathway. Although the activation SK3 and IK1 converges on EDH, their subcellular effects signal transduction are different not completely clear. In this study, a novel endothelium-specific knockout (SK3(-/-)) mouse model was utilized to specifically examine contribution mesenteric...
Acid-sensing ion channels (ASICs) are the major proton receptor in brain and a key mediator of acidosis-induced neuronal injuries disease. Most published data on ASIC function came from studies performed mice, relatively little is known about potential differences between human mouse ASICs (hASIC mASIC, respectively). This information critical for us to better interpret functional importance Here, we examined expression acutely resected cortical tissue. Compared with cortex, tissue showed...
Patients with nosocomial pneumonia exhibit elevated levels of neurotoxic amyloid and tau proteins in the cerebrospinal fluid (CSF). In vitro studies indicate that pulmonary endothelium infected clinical isolates either Pseudomonas aeruginosa, Klebsiella pneumoniae, or Staphylococcus aureus produces releases cytotoxic proteins. However, effects endothelium-derived on brain function have not been elucidated. Here, we show P. aeruginosa infection elicits accumulation detergent insoluble protein...
Mesenteric artery endothelium expresses both small (SK3)- and intermediate (IK1)-conductance Ca2+-activated K+ (KCa) channels whose activity modulates vascular tone via endothelium-dependent hyperpolarization (EDH). Two other major vasodilation pathways utilize nitric oxide (NO) prostacyclin (PGI2). To examine how ovariectomy (ovx) affects the basal acetylcholine (ACh)-induced of each these three to vasorelaxation, we used wire myograph electrophysiological recordings. The results from...
Abstract Increased neural activities reduced pH at the synaptic cleft and interstitial spaces. Recent studies have shown that protons function as a neurotransmitter. However, it remains unclear whether signal through metabotropic receptor to regulate function. Here, we showed GPR68, proton-sensitive GPCR, exhibited wide expression in hippocampus, with higher observed CA3 pyramidal neurons dentate granule cells. In organotypic hippocampal slice neurons, ectopically expressed GPR68-GFP was...
Small- and intermediate-conductance Ca 2+ -activated K + channels (SK3/Kcnn3 IK1/Kcnn4) are expressed in vascular endothelium. Their activities play important roles regulating tone through their modulation of intracellular concentration ([Ca ] i ) required for the production endothelium-derived vasoactive agents. Activation endothelial IK1 or SK3 hyperpolarizes cell membrane potential, increases influx, leads to release factors, thereby impacting blood pressure. To examine distinct channels,...
In ovine basilar arterial smooth muscle cells (SMCs), the fetal "big" Ca2+-activated K+ (BK) channel activity is significantly greater and has a lower Ca2+ setpoint than BK channels from adult cells. present study, we tested hypothesis that these differences result developmentally regulated phosphorylation of channels. Using patch-clamp technique novel in situ enzymological approach, measured rates extents changes voltage activation SMC inside-out patch preparations response to selective...
Large-conductance Ca2+-sensitive K+ (BK) channel activity is greater in basilar artery smooth muscle cells (SMCs) of the fetus than adult, and this increased associated with a lower BK Ca2+ set point (Ca0). Associated PKG three times channels from fetal adult myocytes, whereas PKA myocytes. We hypothesized that change Ca0 during development results different levels phosphorylation. In inside-out membrane patch preparations SMCs sheep, we measured four states phosphorylation: native,...
Bacterial pneumonia and sepsis are both common causes of end-organ dysfunction, especially in immunocompromised critically ill patients. Pre-clinical data demonstrate that bacterial elicit the production cytotoxic tau amyloids from pulmonary endothelial cells, which cause lung brain injury naïve animal subjects, independent primary infection. The contribution infection-elicited to dysfunction has not been examined clinical setting. We hypothesized present bronchoalveolar lavage fluid...
Acclimatization to high-altitude, long-term hypoxia (LTH) reportedly alters cerebral artery contraction-relaxation responses associated with changes in K(+) channel activity. We hypothesized that maintain oxygenation during LTH, basilar arteries (BA) the ovine adult and near-term fetus would show increased large-conductance Ca(2+) activated potassium (BK) measured BK activity, expression, cell surface distribution by use of patch-clamp electrophysiology, flow cytometry, confocal microscopy,...