A5079621764- Ion channel regulation and function
- Neurobiology and Insect Physiology Research
- Adipose Tissue and Metabolism
- Neuroscience and Neural Engineering
- Ion Channels and Receptors
- Exercise and Physiological Responses
- Cardiac electrophysiology and arrhythmias
- Muscle Physiology and Disorders
- Muscle activation and electromyography studies
- Cellular transport and secretion
- Cardiovascular Effects of Exercise
- Genetic Neurodegenerative Diseases
- Anesthesia and Neurotoxicity Research
- Neuroscience and Neuropharmacology Research
- Nitric Oxide and Endothelin Effects
- Mitochondrial Function and Pathology
- Neuroinflammation and Neurodegeneration Mechanisms
- Ion Transport and Channel Regulation
- Flavonoids in Medical Research
- Cardiovascular and exercise physiology
- 3D Printing in Biomedical Research
- Erythrocyte Function and Pathophysiology
- Advanced Sensor and Energy Harvesting Materials
- Advanced Fluorescence Microscopy Techniques
- Toxin Mechanisms and Immunotoxins
University of Otago
2022-2024
Baylor College of Medicine
2018-2020
The University of Queensland
2010-2019
Store-operated Ca(2+) entry (SOCE) is an important mechanism in virtually all cells. In adult skeletal muscle, this highly specialized for the rapid delivery of from transverse tubule into junctional cleft during periods depleting release. dystrophic muscle fibers, SOCE may be a source overload, leading to cell necrosis. However, possibility yet examined fiber To examine this, tubular system and cytoplasm were simultaneously imaged direct release sarcoplasmic reticulum (SR) fibers healthy...
Ephrin (Eph) signaling within the central nervous system is known to modulate axon guidance, synaptic plasticity, and promote long-term potentiation. We investigated potential involvement of EphA2 receptors in ischemic stroke-induced brain inflammation a mouse model focal stroke. Cerebral ischemia was induced male C57Bl6/J wild-type (WT) EphA2-deficient (EphA2−/−) mice by middle cerebral artery occlusion (MCAO; 60 min), followed reperfusion (24 or 72 h). Brain infarction measured using...
Skeletal muscle from mdx mice is characterized by increased Nox2 ROS, altered microtubule network, stiffness, and decreased muscle/respiratory function. While de-tyrosination has been suggested to increase stiffness ROS production in isolated single myofibers, its role altering tissue function not established. Because upregulated prior network alterations affect formation, we investigated the of diaphragm organization, Eliminating prevents disorganization reduces fibrosis diaphragm. Fibrosis...
Key points Current methods do not allow a quantitative description of Ca 2+ movements across the tubular (t‐) system membrane without isolating membranes from their native skeletal muscle fibre. Here we present fluorescence‐based method that allows determination t‐system [Ca ] transients and derivation fluxes in mechanically skinned fibres. Differences ‐handling properties between fast‐ slow‐twitch fibres rat are resolved for first time using this new technique. The can be used to study...
Abstract High-force eccentric exercise results in sustained increases cytoplasmic Ca 2+ levels ([Ca ] cyto ), which can cause damage to the muscle. Here we report that a heavy-load strength training bout greatly alters structure of membrane network inside fibres, tubular (t-) system, causing loss its predominantly transverse organization and an increase vacuolation longitudinal tubules across adjacent sarcomeres. The vacuoles displayed distinct -handling properties. Both t-system components...
We used the nanometer-wide tubules of transverse tubular (t)-system human skeletal muscle fibers as sensitive sensors for quantitative monitoring Ca2+-handling properties in narrow junctional cytoplasmic space sandwiched between membrane and sarcoplasmic reticulum cisternae single fibers. The t-system sealed with a Ca2+-sensitive dye trapped it is to changes ryanodine receptor (RyR) Ca2+ leak, store operated calcium entry flux, plasma Ca pump, sodium-calcium exchanger activities, thus making...
The ability for skeletal muscle to perform optimally can be affected by the regulation of Ca2+ within triadic junctional space at rest. Reactive oxygen species impact performance due changes in oxidative stress, damage and redox signaling cascades. interplay between ROS triad is therefore important understand as it healthy diseased muscle. Here, we aimed examine how micro-domain mouse fibre alters homeostasis these complexes. dystrophic mdx model displays increased RyR1 leak NAD(P)H Oxidase...
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Fast-twitch skeletal muscle fibers are often exposed to motor neuron double discharges (≥200 Hz), which markedly increase both the rate of contraction and magnitude resulting force responses. However, mechanism responsible for these effects is poorly understood, likely because technical limitations in previous studies. In this study, we measured cytosolic Ca2+ during doublet activation using low-affinity indicator Mag-Fluo-4 at high temporal resolution modeled stimulation on sarcoplasmic...
Non‐technical summary Contraction of the vertebrate skeletal muscle is dependent on excitation highly specialized plasma membrane individual fibres. Most covers an extensive, structured network narrow invaginating tubules, but little known about how propagates along tubular mammalian fibres in radial and longitudinal directions with respect to fibre axis. Here we show that can take multiple pathways through internal tubules fast‐twitch rat determine rates spread within internalized this...
The majority of the skeletal muscle plasma membrane is internalized as part tubular (t-) system, forming a standing junction with sarcoplasmic reticulum (SR) throughout fiber. This arrangement facilitates not only rapid and large release Ca(2+) from SR for contraction upon excitation fiber, but has also direct implications other interdependent cellular regulators Ca(2+). t-system Ca-ATPase (PMCA) store-operated entry (SOCE) can be activated In muscle, sensor responsible rapidly SOCE appears...
Skeletal muscle fibres are large and highly elongated cells specialized for producing the force required posture movement. The process of controlling production within muscle, known as excitation-contraction coupling, requires virtually simultaneous release amounts Ca(2+) from sarcoplasmic reticulum (SR) at level every sarcomere fibre. Here we imaged movements SR, tubular (t-) system in cytoplasm to observe that SR skeletal is a connected network capable allowing diffusion its lumen promote...
The mouse model of Duchenne muscular dystrophy, the mdx mouse, displays changes in Ca 2+ homeostasis that may lead to pathology muscle. Here we examine activation store overload-induced release (SOICR) SOICR is associated with depolymerization sarcoplasmic reticulum (SR) buffer calsequestrin and reduction SR buffering power (B ). role healthy dystrophic muscle unclear. Using skinned fibers show lowering Mg concentration can activate discrete events did not necessarily SOICR. However, waves...
The complex membrane structure of the tubular system (t-system) in skeletal muscle fibers is open to extracellular environment, which prevents measurements H+ movement across its interface with cytoplasm by conventional methods. Consequently, little known about t-system’s role regulation cytoplasmic pH, different from pH. Here we describe a novel approach measure H+-flux t-system fast-twitch under conditions. involves loading intact rat strong pH buffer (20 mM HEPES) and pH-sensitive...
The cGMP-dependent protein kinase G (PKG) phosphorylates the cardiac ryanodine receptor (RyR2) in vitro. We aimed to determine whether modulation of endogenous PKG alters RyR2-mediated spontaneous Ca2+ release and this effect is linked a change RyR2 phosphorylation.& Results: Human embryonic kidney (HEK293) cells with inducible expression were treated cGMP analogue 8-Br-cGMP (100 μM) activate PKG. In transfected luminal sensor, D1ER, activation significantly reduced threshold for (93.9 ±...
Key points We developed a method that allows for real‐time assessment of cellular metabolism in isolated, intact long skeletal muscle fibre bundles from adult mice. This can be used to study changes mitochondrial function and fuel utilisation live bundles. Our enables flexibility experimental design high‐throughput parameters isolated Extensor digitorum longus (EDL) obtained chronic high‐fat diet fed mice had lower basal oxygen consumption under FCCP‐induced maximal respiration, when...