Reverse mode Na+/Ca2+ exchange mediated by STIM1 contributes to Ca2+ influx in airway smooth muscle following agonist stimulation

<p>Abstract</p> <p>Background</p> <p>Agonist stimulation of airway smooth muscle (ASM) results in IP₃mediated Ca²⁺release from the sarcoplasmic reticulum followed by the activation of store operated and receptor operated non-selective cation channels. Activation of these non-selective channels also results in a Na⁺influx. This localised increase in Na⁺levels can potentially switch the Na⁺/Ca²⁺exchanger into reverse mode and so result in a further influx of Ca²⁺. The aim of this study was to characterise the expression and physiological function of the Na⁺/Ca²⁺exchanger in cultured human bronchial smooth muscle cells and determine its contribution to agonist induced Ca²⁺influx into these cells.</p> <p>Methods</p> <p>The expression profile of NCX (which encodes the Na⁺/Ca²⁺exchanger) homologues in cultured human bronchial smooth muscle cells was determined by reverse transcriptase PCR. The functional activity of reverse mode NCX was investigated using a combination of whole cell patch clamp, intracellular Ca²⁺measurements and porcine airway contractile analyses. KB-R7943 (an antagonist for reverse mode NCX) and target specific siRNA were utilised as tools to inhibit NCX function.</p> <p>Results</p> <p>NCX1 protein was detected in cultured human bronchial smooth muscle cells (HBSMC) cells and NCX1.3 was the only mRNA transcript variant detected. A combination of intracellular Na⁺loading and addition of extracellular Ca²⁺induced an outwardly rectifying current which was augmented following stimulation with histamine. This outwardly rectifying current was inhibited by 10 μM KB-R7943 (an antagonist of reverse mode NCX1) and was reduced in cells incubated with siRNA against NCX1. Interestingly, this outwardly rectifying current was also inhibited following knockdown of STIM1, suggesting for the first time a link between store operated cation entry and NCX1 activation. In addition, 10 μM KB-R7943 inhibited agonist induced changes in cytosolic Ca²⁺and induced relaxation of porcine peripheral airways.</p> <p>Conclusions</p> <p>Taken together, these data demonstrate a potentially important role for NCX1 in control of Ca²⁺homeostasis and link store depletion via STIM1 directly with NCX activation.</p

Structural and electrical characterization of AuPtAlTi ohmic contacts to AlGaN/GaN with varying annealing temperature and Al content

The effect of varying annealing temperature and Al layer thickness on the structural and electrical characteristics of AuPtAlTi/AlGaN/GaN ohmic contact structures has been systematically investigated. The relationship between annealing temperature, Al content, interfacial microstructure, surface planarity and contact resistance is examined. In particular, the presence of a detrimental low temperature Pt-Al reaction is identified. This is implicated in both the requirement for a higher Al:Ti ratio than is required for related AuPdAlTi contact schemes and through the degraded temperature dependent resistance behaviour of the annealed AuPtAlTi contacts

Function and fate of myofibroblasts after myocardial infarction.

The importance of cardiac fibroblasts in the regulation of myocardial remodelling following myocardial infarction (MI) is becoming increasingly recognised. Studies over the last few decades have reinforced the concept that cardiac fibroblasts are much more than simple homeostatic regulators of extracellular matrix turnover, but are integrally involved in all aspects of the repair and remodelling of the heart that occurs following MI. The plasticity of fibroblasts is due in part to their ability to undergo differentiation into myofibroblasts. Myofibroblasts are specialised cells that possess a more contractile and synthetic phenotype than fibroblasts, enabling them to effectively repair and remodel the cardiac interstitium to manage the local devastation caused by MI. However, in addition to their key role in cardiac restoration and healing, persistence of myofibroblast activation can drive pathological fibrosis, resulting in arrhythmias, myocardial stiffness and progression to heart failure. The aim of this review is to give an appreciation of both the beneficial and detrimental roles of the myofibroblast in the remodelling heart, to describe some of the major regulatory mechanisms controlling myofibroblast differentiation including recent advances in the microRNA field, and to consider how this cell type could be exploited therapeutically

A hybrid simulation technique for electrothermal studies of two-dimensional GaN-on-SiC high electron mobility transistors

In this work, a hybrid simulation technique is introduced for the electrothermal study of a two-dimensional GaN-on-SiC high electron mobility transistor. Detailed electron and phonon transport is considered by coupled electron and phonon Monte Carlo simulations in the transistor region. For regions away from the transistor, the conventional Fourier's law is used for thermal analysis to minimize the computational load. This hybrid simulation strategy can incorporate the physical phenomena over multiple length scales, including phonon generation by hot electrons in the conduction channel, frequency-dependent phonon transport in the transistor region, and heat transfer across the whole macroscale device. Published by AIP Publishing.Defense Advanced Research Agency (DARPA) [FA8650-15-1-7523]12 month embargo; published online 22 May 2017This item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at [email protected]