A5002065730- Ion channel regulation and function
- Cardiac electrophysiology and arrhythmias
- Neuroscience and Neural Engineering
- Neuroscience and Neuropharmacology Research
- Receptor Mechanisms and Signaling
- Nicotinic Acetylcholine Receptors Study
- Blood Pressure and Hypertension Studies
- Cardiomyopathy and Myosin Studies
- Pharmaceutical industry and healthcare
- Neurobiology and Insect Physiology Research
- Ion Transport and Channel Regulation
- Hormonal Regulation and Hypertension
- Pain Mechanisms and Treatments
- Cardiovascular Effects of Exercise
- Cardiac Arrhythmias and Treatments
- Calcium signaling and nucleotide metabolism
- Electrochemical Analysis and Applications
- Erythrocyte Function and Pathophysiology
- Sperm and Testicular Function
- Medicinal Plants and Neuroprotection
- Medication Adherence and Compliance
- Cellular Mechanics and Interactions
- Cardiac Fibrosis and Remodeling
- Machine Learning in Bioinformatics
- Erythropoietin and Anemia Treatment
University of Edinburgh
2004-2022
National University of Luján
2018
Consejo Nacional de Investigaciones Científicas y Técnicas
2018
The Queen's Medical Research Institute
2010-2017
The University of Texas MD Anderson Cancer Center
2007
University of Manchester
2000-2006
Institut Pasteur de Montevideo
2002
University of Liverpool
1995-2000
Instituto de Estudios Avanzados
1997-1998
Cornell University
1996
The aim of this work was to investigate whether beat-to-beat alternation in the amplitude systolic Ca(2+) transient (Ca(2+) alternans) is due changes sarcoplasmic reticulum (SR) content, and if so, alternans arises a change gain feedback controlling SR content. We found that, rat ventricular myocytes, stimulating with small (20 mV) depolarizing pulses produced transient. Confocal measurements showed that larger transients resulted from propagation waves. content (measured caffeine-evoked...
Intracellular calcium concentration ([Ca 2+ ] i ) and Na + –Ca exchange currents were measured in calcium‐overloaded voltage‐clamped rat ventricular myocytes loaded with the Ca sensitive fluorescent indicator indo‐1. Sarcoplasmic reticulum (SR) content was from integral of caffeineevoked current. In cells that had spontaneous SR release 1 m external o ), raising [Ca increased frequency no effect on content. quiescent cells, produced associated Further increase The amount leaving cell during...
Abstract Perivascular mesenchymal precursor cells (i.e., pericytes) reside in skeletal muscle where they contribute to myofiber regeneration; however, the existence of similar microvessel-associated regenerative cardiac has not yet been documented. We tested whether microvascular pericytes within human myocardium exhibit phenotypes and multipotency their anatomically developmentally distinct counterparts. Fetal adult heart (hHPs) express canonical pericyte markers situ, including CD146, NG2,...
1 The effects of modulating Ca2+-induced Ca2+ release (CICR) in single cardiac myocytes were investigated using low concentrations caffeine (< 500 μm) reduced external (0.5 mm). Caffeine produced a transient potentiation systolic [Ca2+]i (to 800 % control) which decayed back to control levels. 2 decreased the steady-state sarcoplasmic reticulum (SR) content. As concentration was increased, both and decrease SR content increased. At higher concentrations, potentiating effect more rapidly but...
Sarcoplasmic reticulum (SR) Ca2+ release, through the ryanodine receptor (RyR), is essential for systolic transient and thus cardiac contractile function. The aim of this study was to examine effects on spatial organization depressing RyR open probability (P(o)) with tetracaine or intracellular acidification. Voltage-clamped, fluo-3-loaded myocytes were studied using confocal microscopy. Depressing P(o) increased variability amplitude between different regions cell. This often produced...
Abstract —The aim of this study was to investigate how sarcoplasmic reticulum (SR) Ca 2+ content and systolic are controlled when entry into the cell is varied. Experiments were performed on voltage-clamped rat ferret ventricular myocytes loaded with fluo-3 measure intracellular concentration ([Ca ] i ). Increasing external o ) from 1 2 mmol/L increased amplitude transient no effect SR content. This constancy shown result because larger activates a efflux that balances influx. Decreasing [Ca...
[Ca2+]i was measured using the fluorescent indicator indo 1 in voltage-clamped ferret and rat ventricular myocytes. The Ca2+ content of sarcoplasmic reticulum (SR) estimated from integral Na(+)-Ca2+ exchange current activated by caffeine. Refilling SR after caffeine removal enhanced stimulation. As systolic transient recovered, L-type decreased that tail increased. For early pulses, gain via is greater than loss exchanger, during steady state stimulation, fluxes are equal. difference...
1. The aim of these experiments was to compare the time course changes in intracellular Ca2+ concentration ([Ca2+]i) measured bulk cytoplasm with those estimated occur near sarcolemma. Sarcolemmal Na(+)‐Ca2+ exchange current and [Ca2+]i were single, voltage‐clamped ventricular myocytes. 2. Spontaneous release from sarcoplasmic reticulum (SR) resulted a transient inward current. This developed decayed more quickly than accompanying (measured indo‐1) resulting hysteresis between A similar also...
The aim of this work was to investigate whether it is possible remove arrhythmogenic Ca 2+ release from the sarcoplasmic reticulum that occurs in calcium overload without compromising normal systolic release. Exposure rat ventricular myocytes isoproterenol (1 μmol/L) resulted an increased amplitude transient and appearance waves diastolic Application tetracaine (25 50 decreased frequency or abolished This accompanied by increase transient. Cellular flux balance investigated integrating entry...
Recent work has identified reductions in the systolic Ca(2+) transient cardiac disease states. The aim of present study was to identify mechanisms responsible for perturbations intracellular calcium homeostasis isolated myocytes and determine if such changes can quantitatively explain reduced transient.Left ventricular hypertrophy (LVH) induced by aortic coarctation adult ferrets. Changes regulation, sarcolemmal fluxes SR function were measured single left myocytes.Cardiac associated with a...
Previous work has shown that small depolarizing pulses produce a beat to alternation in the amplitude of systolic Ca(2+) transient ventricular myocytes. The aim present was investigate role changes SR content and L-type current this alternans. As pulse increased from 10 30 mV magnitude alternans decreased. Confocal linescan studies showed accompanied by an increase number sites which waves propagated. A sudden decrease depolarisation resulted three classes behaviour: (1) gradual before...
Mechanical alternans in cardiac muscle is associated with intracellular Ca(2+) alternans. Mechanisms underlying are unclear. In previous experimental studies, we produced of systolic under voltage clamp, either by partially inhibiting the release mechanism, or applying small depolarizing pulses. each case, relied on propagating waves release. The aim this study to investigate computer modeling how produced. A mathematical model a cell 75 coupled elements developed, element contains L-type...
Obesity and hypertension are 2 major health issues of the 21st century. The syndrome apparent mineralocorticoid excess is caused by deficiency 11β-hydroxysteroid dehydrogenase type (Hsd11b2), which normally inactivates glucocorticoids, rendering receptor aldosterone-specific. metabolic consequences Hsd11b2 knockout in rat investigated parallel with electrolyte homeostasis. was knocked out, pronuclear microinjection targeted zinc-finger nuclease mRNAs, 1 line characterized for its response to...
To examine the possible cardiotoxicity of antimalarial drug mefloquine, increasing doses (0.3–30 mg kg −1 ) were given i.v. to anaesthetized guinea‐pigs. Mefloquine did not alter ECG intervals significantly but gradually increased systolic blood pressure (at 3 then had a depressor effect 10 ). Death due profound hypotension, probably resulting from cardiac contractile failure or AV block, occurred after either (2/6) 30 (4/6) mefloquine. In isolated preparations mefloquine (3–100 μ M...
Corticosteroids directly affect the heart and vasculature are implicated in pathogenesis of failure. Attention is focussed upon role mineralocorticoid receptor (MR) mediating pro-fibrotic other adverse effects corticosteroids heart. In contrast, glucocorticoid (GR) less well understood. We addressed this mice with cardiomyocyte vascular smooth muscle deletion GR (SMGRKO mice). Survival SMGRKO to weaning was reduced compared that littermate controls. Doppler measurements blood flow across...
Crustacean cardioactive peptide (CCAP) and related peptides are multifunctional regulatory neurohormones found in invertebrates. We isolated a CCAP-related (conoCAP-a, for cone snail CardioActive Peptide) cloned the cDNA of its precursor from venom Conus villepinii. The conoCAP-a encodes two additional CCAP-like peptides: conoCAP-b conoCAP-c. This multi-peptide organization is analogous to recently predicted molluscan preprohormones, suggests mechanism generation biological diversification...